トップ›研究者一覧›松本真司

研究者を探す

研究者にアプローチする
更新情報を通知する

松本真司

徳島大学

プロフィール
教育活動
研究活動
社会活動
リサーチマップ・
Jグローバル
KAKEN
注目研究

研究者総覧で最新データを確認する

2024年10月23日更新

職名: 教授
電話: 088-633-7323
電子メール: smatsumoto@tokushima-u.ac.jp
学歴: 2005/3: 広島大学歯学部歯学科卒業
2009/3: 広島大学大学院医歯薬学総合研究科創生医科学専攻博士課程終了
学位: 博士(歯学) (2009年3月)
職歴・経歴: 2009/4: 広島大学大学院医歯薬学総合研究科分子細胞情報学博士研究員
2009/12: 大阪大学大学院医学系研究科分子病態生化学特任研究員
2012/4: 大阪大学大学院医学系研究科分子病態生化学特任助教(常勤)
2016/4: 大阪大学大学院医学系研究科分子病態生化学助教
2021/4: 大阪大学大学院医学系研究科分子病態生化学准教授
2023/4: 大阪大学感染症総合教育研究拠点特任准教授(常勤)

専門分野・研究分野: 生理学 (Physiology)
口腔分子生理学 (Molecular Oral Physiology)
分子細胞生物学 (Molecular and Cellular Biology)
分子腫瘍学 (Molecular Oncology)

研究者総覧で最新データを確認する

2024年10月23日更新

専門分野・研究分野: 生理学 (Physiology)
口腔分子生理学 (Molecular Oral Physiology)
分子細胞生物学 (Molecular and Cellular Biology)
分子腫瘍学 (Molecular Oncology)
担当経験のある授業科目: (基礎系)国家試験・CBT対策講義 (学部)
口腔分子生理学 (大学院)
口腔分子生理学演習 (大学院)
口腔生理学 (学部)
基礎生物学DⅡ (共通教育)
小児口腔保健学 (大学院)
生理学 (学部)
生理学・口腔生理学実習 (学部)
生理学・生化学・病理学・薬理学 (学部)
統合生理・口腔生理学 (学部)
指導経験: 研究者総覧に該当データはありませんでした。

研究者総覧で最新データを確認する

2024年10月23日更新

専門分野・研究分野: 生理学 (Physiology)
口腔分子生理学 (Molecular Oral Physiology)
分子細胞生物学 (Molecular and Cellular Biology)
分子腫瘍学 (Molecular Oncology)

研究テーマ: 上皮組織の形成と機能獲得機序の解明, 上皮組織の腫瘍形成機序の解明と治療薬開発 (上皮組織形成, 腫瘍形成, 核酸医薬, Wntシグナル, 唾液腺)

著書

松本真司 :
Wnt経路:がんゲノムペディア,
羊土社, 2024年1月. 木村公一, 松本真司, 菊池章 :
Wnt シグナル:がん生物学イラストレイテッド第2版,
羊土社, 2019年. 菊池章, 松本真司 :
Hippoシグナル:サイトカイン・増殖因子キーワード事典,
羊土社, 2015年. Akira Kikuchi, Shinji Matsumoto, Katsumi Fumoto and Akira Sato :
Modulation of Wnt Signaling by Endocytosis of Receptor Complexes,
John Wiley & Sons, Inc., 2014.

(要約): Summary Current evidence suggests that in addition to the specific combination of Wnt ligands and receptors, endocytosis of the Wnt-receptor complex, binding of Wnt to heparan sulfate proteoglycans (HSPGs), and ubiquitination of Wnt receptors are involved in the regulation of the Wnt signaling pathway. This chapter highlights new insight into the mechanisms of Wnt signaling pathway activation, which occurs on and inside the cell surface membrane. There are two different types of endocytosis, clathrin-mediated endocytosis and caveolin-mediated endocytosis. Clathrin and caveolin play a major role in the respective pathways. Compared with the controversial roles of endocytic pathways in the β-catenin-dependent pathway, the importance of endocytosis in the β-catenin-independent pathway is well documented.

菊池章, 松本真司 :
細胞増殖・運動・死とがん:プログレッシブ生命科学,
南山堂, 2014年. 菊池章, 松本真司 :
Wntシグナル:がん生物学イラストレイテッド第1版,
羊土社, 2011年.

論文

Hideki Yamamoto, Ryota Sada, Akikazu Harada, Shinji Matsumoto and Akira Kikuchi :
Annexin A2 mediates plasma membrane localization of CKAP4, a dickkopf1 receptor, in cancer cells.,
Journal of Cell Science, Vol.in press, 2024. Ryota Sada, Hideki Yamamoto, Shinji Matsumoto, Akikazu Harada and Akira Kikuchi :
Newly developed humanized anti-CKAP4 antibody suppresses pancreatic cancer growth by inhibiting DKK1-CKAP4 signaling.,
Cancer Science, Vol.115, No.10, 3358-3369, 2024.

(要約): Cytoskeleton-associated protein 4 (CKAP4) is a cell surface receptor for Dickkopf 1 (DKK1), a secreted protein. The DKK1-CKAP4 pathway is activated in various malignant tumors, including pancreatic, lung, esophageal, and liver cancers, to promote tumor growth. Thus, CKAP4 has been expected to represent a novel molecular target of cancer therapy. Recombinant mouse anti-CKAP4 antibodies were generated based on an original mouse antibody (3F11-2B10) and inhibited DKK1-CKAP4 signaling and xenograft tumor formation induced by pancreatic cancer cells, which was comparable with 3F11-2B10. From the 3F11-2B10 nucleotide sequence, humanized anti-CKAP4 antibody (Hv1Lt1) was subsequently developed. The binding affinity of Hv1Lt1 for CKAP4 was superior to that of 3F11-2B10. Hv1Lt1 inhibited DKK1 binding to CKAP4, AKT activity, and sphere formation of pancreatic cancer cells, which was comparable with 3F11-2B10. Hv1Lt1 also suppressed xenograft tumor formation induced by human pancreatic cancer cells and tumor growth in murine cancer models, in which murine pancreatic cancer organoids were orthotopically transplanted into the pancreas. In resected tumor samples from mice treated with Hv1Lt1, anti-tumor immune reactions were modulated and cytotoxic T cells were highly infiltrated in the tumor microenvironment. Additionally, combination of Hv1Lt1 and other chemotherapy drugs exhibited stronger effects compared with monotherapy. These results suggest that Hv1Lt1 represents a promising anti-cancer therapy.
(出版サイトへのリンク): ● Publication site (DOI): 10.1111/cas.16278
(文献検索サイトへのリンク): ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 39118263; ● Search Scopus @ Elsevier (PMID): 39118263; ● Search Scopus @ Elsevier (DOI): 10.1111/cas.16278

(DOI: 10.1111/cas.16278, PubMed: 39118263) Koei Shinzawa, Shinji Matsumoto, Ryota Sada, Akikazu Harada, Kaori Saitoh, Keiko Kato, Satsuki Ikeda, Akiyoshi Hirayama, Kazunori Yokoi, Atsushi Tanemura, Keisuke Nimura, Masahito Ikawa, Tomoyoshi Soga and Akira Kikuchi :
GREB1 isoform 4 is specifically transcribed by MITF and required for melanoma proliferation.,
Oncogene, Vol.42, No.42, 3142-3156, 2023.

(要約): Growth regulation by estrogen in breast cancer 1 (GREB1) is involved in hormone-dependent and -independent tumor development (e.g., hepatoblastoma). In this study, we found that a GREB1 splicing variant, isoform 4 (Is4), which encodes C-terminal half of full-length GREB1, is specifically expressed via microphthalmia-associated transcription factor (MITF) in melanocytic melanoma, and that two MITF-binding E-box CANNTG motifs at the 5'-upstream region of GREB1 exon 19 are necessary for GREB1 Is4 transcription. MITF and GREB1 Is4 were strongly co-expressed in approximately 20% of the melanoma specimens evaluated (17/89 cases) and their expression was associated with tumor thickness. GREB1 Is4 silencing reduced melanoma cell proliferation in association with altered expression of cell proliferation-related genes in vitro. In addition, GREB1 Is4 targeting by antisense oligonucleotide (ASO) decreased melanoma xenograft tumor formation and GREB1 Is4 expression in a BRAF; PTEN melanoma mouse model promoted melanoma formation, demonstrating the crucial role of GREB1 Is4 for melanoma proliferation in vivo. GREB1 Is4 bound to CAD, the rate-limiting enzyme of pyrimidine metabolism, and metabolic flux analysis revealed that GREBI Is4 is necessary for pyrimidine synthesis. These results suggest that MITF-dependent GREB1 Is4 expression leads to melanoma proliferation and GREB1 Is4 represents a new molecular target in melanoma.
(キーワード): Animals / Mice / Humans / Microphthalmia-Associated Transcription Factor / Cell Line, Tumor / Melanoma / Protein Isoforms / Cell Proliferation / Pyrimidines / Gene Expression Regulation, Neoplastic / Neoplasm Proteins
(出版サイトへのリンク): ● Publication site (DOI): 10.1038/s41388-023-02803-6
(文献検索サイトへのリンク): ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 37658191; ● Search Scopus @ Elsevier (PMID): 37658191; ● Search Scopus @ Elsevier (DOI): 10.1038/s41388-023-02803-6

(DOI: 10.1038/s41388-023-02803-6, PubMed: 37658191) Shinji Matsumoto, Akikazu Harada, Minami Seta, Masayuki Akita, Hidetoshi Gon, Takumi Fukumoto and Akira Kikuchi :
Wnt Signaling Stimulates Cooperation between GREB1 and HNF4α to Promote Proliferation in Hepatocellular Carcinoma.,
Cancer Research, Vol.83, No.14, 2312-2327, 2023.

(要約): GREB1 is a liver cancer-specific Wnt signaling target gene that induces an oncogenic shift of HNF4α, a putative tumor suppressor, and may represent a therapeutic target in Wnt-activated hepatocellular carcinoma.
(キーワード): Humans / Carcinoma, Hepatocellular / Liver Neoplasms / Wnt Signaling Pathway / Transcription Factors / Cell Proliferation / Cell Line, Tumor / Gene Expression Regulation, Neoplastic / Neoplasm Proteins
(出版サイトへのリンク): ● Publication site (DOI): 10.1158/0008-5472.CAN-22-3518
(文献検索サイトへのリンク): ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 37347203; ● Search Scopus @ Elsevier (PMID): 37347203; ● Search Scopus @ Elsevier (DOI): 10.1158/0008-5472.CAN-22-3518

(DOI: 10.1158/0008-5472.CAN-22-3518, PubMed: 37347203) Hiroshi Kishimoto, Masayoshi Iwasaki, Kensaku Wada, Keita Horitani, Osamu Tsukamoto, Kenta Kamikubo, Seitaro Nomura, Shinji Matsumoto, Takeshi Harada, Daisuke Motooka, Daisuke Okuzaki, Seiji Takashima, Issei Komuro, Akira Kikuchi and Ichiro Shiojima :
Wnt5a-YAP signaling axis mediates mechanotransduction in cardiac myocytes and contributes to contractile dysfunction induced by pressure overload.,
iScience, Vol.26, No.7, 107146, 2023.

(要約): These results collectively suggest that Wnt5a-YAP signaling axis mediates mechanotransduction in cardiomyocytes and contributes to heart failure progression.
(出版サイトへのリンク): ● Publication site (DOI): 10.1016/j.isci.2023.107146
(文献検索サイトへのリンク): ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 37456848; ● Search Scopus @ Elsevier (PMID): 37456848; ● Search Scopus @ Elsevier (DOI): 10.1016/j.isci.2023.107146

(DOI: 10.1016/j.isci.2023.107146, PubMed: 37456848) Kosuke Iguchi, Ryota Sada, Shinji Matsumoto, Hirokazu Kimura, Yoh Zen, Masayuki Akita, Hidetoshi Gon, Takumi Fukumoto and Akira Kikuchi :
DKK1-CKAP4 signal axis promotes hepatocellular carcinoma aggressiveness.,
Cancer Science, Vol.114, No.5, 2063-2077, 2023.

(要約): Hepatocellular carcinoma (HCC) is the most prevalent malignant liver neoplasm. Despite the advances in diagnosis and treatment, the prognosis of HCC patients remains poor. Cytoskeleton-associated membrane protein 4 (CKAP4) is a receptor of the glycosylated secretory protein Dickkopf-1 (DKK1), and the DKK1-CKAP4 axis is activated in pancreatic, lung, and esophageal cancer cells. Expression of DKK1 and CKAP4 has been examined in HCC in independent studies that yielded contradictory results. In this study, the relationship between the DKK1-CKAP4 axis and HCC was comprehensively examined. In 412 HCC cases, patients whose tumors were positive for both DKK1 and CKAP4 had a poor prognosis compared to those who were positive for only one of these markers or negative for both. Deletion of either DKK1 or CKAP4 inhibited HCC cell growth. In contrast to WT DKK1, DKK1 lacking the CKAP4 binding region did not rescue the phenotypes caused by DKK1 depletion, suggesting that binding of DKK1 to CKAP4 is required for HCC cell proliferation. Anti-CKAP4 Ab inhibited HCC growth, and its antitumor effect was clearly enhanced when combined with lenvatinib, a multikinase inhibitor. These results indicate that simultaneous expression of DKK1 and CKAP4 is involved in the aggressiveness of HCC, and that the combination of anti-CKAP4 Ab and other therapeutics including lenvatinib could represent a promising strategy for treating advanced HCC.
(キーワード): Humans / Membrane Proteins / Carcinoma, Hepatocellular / Liver Neoplasms / Cytoskeleton / Intercellular Signaling Peptides and Proteins
(出版サイトへのリンク): ● Publication site (DOI): 10.1111/cas.15743
(文献検索サイトへのリンク): ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 36718957; ● CiNii @ 国立情報学研究所 (CRID): 1360580229816409728; ● Summary page in Scopus @ Elsevier: 2-s2.0-85150525190

(DOI: 10.1111/cas.15743, PubMed: 36718957, CiNii: 1360580229816409728, Elsevier: Scopus) Shinsuke Fujii, Takuma Ishibashi, Megumi Kokura, Tatsufumi Fujimoto, Shinji Matsumoto, Satsuki Shidara, J Kari Kurppa, Judith Pape, Javier Caton, R Peter Morgan, Kristiina Heikinheimo, Akira Kikuchi, Eijiro Jimi and Tamotsu Kiyoshima :
RAF1-MEK/ERK pathway-dependent ARL4C expression promotes ameloblastoma cell proliferation and osteoclast formation.,
The Journal of Pathology, Vol.256, No.1, 119-133, 2021.

(要約): Ameloblastoma is an odontogenic neoplasm characterized by slow intraosseous growth with progressive jaw resorption. Recent reports have revealed that ameloblastoma harbours an oncogenic BRAFV600E mutation with mitogen-activated protein kinase (MAPK) pathway activation and described cases of ameloblastoma harbouring a BRAFV600E mutation in which patients were successfully treated with a BRAF inhibitor. Therefore, the MAPK pathway may be involved in the development of ameloblastoma; however, the precise mechanism by which it induces ameloblastoma is unclear. The expression of ADP-ribosylation factor (ARF)-like 4c (ARL4C), induced by a combination of the EGF-MAPK pathway and Wnt/β-catenin signalling, has been shown to induce epithelial morphogenesis. It was also reported that the overexpression of ARL4C, due to alterations in the EGF/RAS-MAPK pathway and Wnt/β-catenin signalling, promotes tumourigenesis. However, the roles of ARL4C in ameloblastoma are unknown. We investigated the involvement of ARL4C in the development of ameloblastoma. In immunohistochemical analyses of tissue specimens obtained from 38 ameloblastoma patients, ARL4C was hardly detected in non-tumour regions but tumours frequently showed strong expression of ARL4C, along with the expression of both BRAFV600E and RAF1 (also known as C-RAF). Loss-of-function experiments using inhibitors or siRNAs revealed that ARL4C elevation depended on the RAF1-MEK/ERK pathway in ameloblastoma cells. It was also shown that the RAF1-ARL4C and BRAFV600E-MEK/ERK pathways promoted cell proliferation independently. ARL4C-depleted tumour cells (generated by knockdown or knockout) exhibited decreased proliferation and migration capabilities. Finally, when ameloblastoma cells were co-cultured with mouse bone marrow cells and primary osteoblasts, ameloblastoma cells induced osteoclast formation. ARL4C elevation in ameloblastoma further promoted its formation capabilities through the increased RANKL expression of mouse bone marrow cells and/or primary osteoblasts. These results suggest that the RAF1-MEK/ERK-ARL4C axis, which may function in cooperation with the BRAFV600E-MEK/ERK pathway, promotes ameloblastoma development. © 2021 The Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
(キーワード): ADP-Ribosylation Factors / Ameloblastoma / Cell Proliferation / Cell Transformation, Neoplastic / Extracellular Signal-Regulated MAP Kinases / Female / Gene Expression Regulation, Neoplastic / Humans / MAP Kinase Signaling System / Male / Mitogen-Activated Protein Kinase Kinases / Osteoclasts / Protein Serine-Threonine Kinases / Wnt Signaling Pathway
(出版サイトへのリンク): ● Publication site (DOI): 10.1002/path.5814
(文献検索サイトへのリンク): ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 34622442; ● Search Scopus @ Elsevier (PMID): 34622442; ● Search Scopus @ Elsevier (DOI): 10.1002/path.5814

(DOI: 10.1002/path.5814, PubMed: 34622442) Akikazu Harada, Shinji Matsumoto, Yoshiaki Yasumizu, Kensaku Shojima, Toshiyuki Akama, Hidetoshi Eguchi and Akira Kikuchi :
Localization of KRAS downstream target ARL4C to invasive pseudopods accelerates pancreatic cancer cell invasion.,
eLife, Vol.10, e66721, 2021.

(要約): Pancreatic cancer has a high mortality rate due to metastasis. Whereas KRAS is mutated in most pancreatic cancer patients, controlling KRAS or its downstream effectors has not been succeeded clinically. ARL4C is a small G protein whose expression is induced by the Wnt and EGF-RAS pathways. In the present study, we found that ARL4C is frequently overexpressed in pancreatic cancer patients and showed that its localization to invasive pseudopods is required for cancer cell invasion. IQGAP1 was identified as a novel interacting protein for ARL4C. ARL4C recruited IQGAP1 and its downstream effector, MMP14, to invasive pseudopods. Specific localization of ARL4C, IQGAP1, and MMP14 was the active site of invasion, which induced degradation of the extracellular matrix. Moreover, subcutaneously injected antisense oligonucleotide against ARL4C into tumor-bearing mice suppressed metastasis of pancreatic cancer. These results suggest that ARL4C-IQGAP1-MMP14 signaling is activated at invasive pseudopods of pancreatic cancer cells.
(キーワード): ADP-Ribosylation Factors / Aged / Aged, 80 and over / Animals / Female / Gene Expression Regulation, Neoplastic / Humans / Male / Mice / Middle Aged / Neoplasm Invasiveness / Pancreatic Neoplasms / Proto-Oncogene Proteins p21(ras) / Pseudopodia / Tumor Cells, Cultured
(出版サイトへのリンク): ● Publication site (DOI): 10.7554/eLife.66721
(文献検索サイトへのリンク): ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 34590580; ● Search Scopus @ Elsevier (PMID): 34590580; ● Search Scopus @ Elsevier (DOI): 10.7554/eLife.66721

(DOI: 10.7554/eLife.66721, PubMed: 34590580) Yosuke Miyachi, Miki Nishio, Junji Otani, Shinji Matsumoto, Akira Kikuchi, Wah Tak Mak, Tomohiko Maehama and Akira Suzuki :
TAZ inhibits acinar cell differentiation but promotes immature ductal cell proliferation in adult mouse salivary glands.,
Genes to Cells, Vol.26, No.9, 714-726, 2021.

(要約): There are currently no treatments for salivary gland diseases, making it vital to understand signaling mechanisms operating in acinar and ductal cells so as to develop regenerative therapies. To date, little work has focused on elucidating the signaling cascades controlling the differentiation of these cell types in adult mammals. To analyze the function of the Hippo-TAZ/YAP1 pathway in adult mouse salivary glands, we generated adMOB1DKO mice in which both MOB1A and MOB1B were TAM-inducibly deleted when the animals were adults. Three weeks after TAM treatment, adMOB1DKO mice exhibited smaller submandibular glands (SMGs) than controls with a decreased number of acinar cells and an increased number of immature dysplastic ductal cells. The mutants suffered from reduced saliva production accompanied by mild inflammatory cell infiltration and fibrosis in SMGs, similar to the Sjogren's syndrome. MOB1-deficient acinar cells showed normal proliferation and apoptosis but decreased differentiation, leading to an increase in acinar/ductal bilineage progenitor cells. These changes were TAZ-dependent but YAP1-independent. Biochemically, MOB1-deficient salivary epithelial cells showed activation of the TAZ/YAP1 and β-catenin in ductal cells, but reduced SOX2 and SOX10 expression in acinar cells. Thus, Hippo-TAZ signaling is critical for proper ductal and acinar cell differentiation and function in adult mice.
(キーワード): Acinar Cells / Adaptor Proteins, Signal Transducing / Animals / Apoptosis / Cell Differentiation / Cell Proliferation / Cells, Cultured / Intracellular Signaling Peptides and Proteins / Mice / Mice, Inbred C57BL / SOXB1 Transcription Factors / Salivary Glands / beta Catenin
(出版サイトへのリンク): ● Publication site (DOI): 10.1111/gtc.12879
(文献検索サイトへのリンク): ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 34142411; ● Search Scopus @ Elsevier (PMID): 34142411; ● Search Scopus @ Elsevier (DOI): 10.1111/gtc.12879

(DOI: 10.1111/gtc.12879, PubMed: 34142411) Takeshi Harada, Ryota Sada, Yoshito Osugi, Shinji Matsumoto, Tomoki Matsuda, Mitsuko Hayashi-Nishino, Takeharu Nagai, Akihiro Harada and Akira Kikuchi :
Palmitoylated CKAP4 regulates mitochondrial functions through an interaction with VDAC2 at ER-mitochondria contact sites.,
Journal of Cell Science, Vol.133, No.21, jcs249045, 2020.

(要約): Cytoskeleton-associated protein 4 (CKAP4) is a palmitoylated type II transmembrane protein localized to the endoplasmic reticulum (ER). Here, we found that knockout (KO) of CKAP4 in HeLaS3 cells induces the alteration of mitochondrial structures and increases the number of ER-mitochondria contact sites. To understand the involvement of CKAP4 in mitochondrial functions, the binding proteins of CKAP4 were explored, enabling identification of the mitochondrial porin voltage-dependent anion-selective channel protein 2 (VDAC2), which is localized to the outer mitochondrial membrane. Palmitoylation at Cys of CKAP4 was required for the binding between CKAP4 and VDAC2. In CKAP4 KO cells, the binding of inositol trisphosphate receptor (IP3R) and VDAC2 was enhanced, the intramitochondrial Ca concentration increased and the mitochondrial membrane potential decreased. In addition, CKAP4 KO decreased the oxidative consumption rate, cancer cell proliferation under low-glucose conditions and xenograft tumor formation. The phenotypes were not rescued by expression of a palmitoylation-deficient CKAP4 mutant. These results suggest that CKAP4 plays a role in maintaining mitochondrial functions through the binding to VDAC2 at ER-mitochondria contact sites and that palmitoylation is required for this novel function of CKAP4.This article has an associated First Person interview with the first author of the paper.
(キーワード): Animals / Endoplasmic Reticulum / HeLa Cells / Humans / Lipoylation / Membrane Proteins / Mitochondria / Mitochondrial Membranes / Voltage-Dependent Anion Channel 2
(出版サイトへのリンク): ● Publication site (DOI): 10.1242/jcs.249045
(文献検索サイトへのリンク): ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 33067255; ● Search Scopus @ Elsevier (PMID): 33067255; ● Search Scopus @ Elsevier (DOI): 10.1242/jcs.249045

(DOI: 10.1242/jcs.249045, PubMed: 33067255) Kana Hasegawa, Shinsuke Fujii, Shinji Matsumoto, Yudai Tajiri, Akira Kikuchi and Tamotsu Kiyoshima :
YAP signaling induces PIEZO1 to promote oral squamous cell carcinoma cell proliferation.,
The Journal of Pathology, Vol.253, No.1, 80-93, 2020.

(要約): entry and cell proliferation in OSCC cells. Experiments using three-dimensional and suspension culture revealed that PIEZO1 was involved in OSCC cellular growth. Finally, YAP overexpression in the nucleus and/or cytoplasm was immunohistochemically detected in tumor lesions with frequent expression of both PIEZO1 and Ki-67, but not in non-tumor regions of OSCC specimens. These results suggest that the YAP/PIEZO1 axis promotes OSCC cell growth. © 2020 The Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
(キーワード): Adaptor Proteins, Signal Transducing / Adult / Aged / Aged, 80 and over / Calcium / Calcium Signaling / Cell Line, Tumor / Cell Proliferation / Female / Gene Expression Regulation, Neoplastic / Humans / Ion Channels / Male / Middle Aged / Mouth Neoplasms / Squamous Cell Carcinoma of Head and Neck / Transcription Factors / YAP-Signaling Proteins
(出版サイトへのリンク): ● Publication site (DOI): 10.1002/path.5553
(文献検索サイトへのリンク): ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 32985688; ● Search Scopus @ Elsevier (PMID): 32985688; ● Search Scopus @ Elsevier (DOI): 10.1002/path.5553

(DOI: 10.1002/path.5553, PubMed: 32985688) Kenji Kimura, Shinji Matsumoto, Takeshi Harada, Eiichi Morii, Izumi Nagatomo, Yasushi Shintani and Akira Kikuchi :
ARL4C is associated with initiation and progression of lung adenocarcinoma and represents a therapeutic target.,
Cancer Science, Vol.111, No.3, 951-961, 2020.

(要約): Lung adenocarcinoma is the most common histological type of lung cancer and is classified into adenocarcinoma in situ (AIS), minimally invasive adenocarcinoma (MIA) and invasive adenocarcinoma (IA). Atypical adenomatous hyperplasia (AAH) lesions are possible precursors to adenocarcinoma. However, the mechanism underlying the stepwise continuum of lung adenocarcinoma is unclear. In this study, the involvement of ADP-ribosylation factor (ARF)-like (ARL) 4C (ARL4C), a member of the small GTP-binding protein family, in the progression of lung adenocarcinoma and the possibility of ARL4C as a molecular target for lung cancer therapy were explored. ARL4C was frequently expressed in AAH and ARL4C expression in immortalized human small airway epithelial cells promoted cell proliferation and suppressed cell death. In addition, ARL4C was expressed with increased frequency in AIS, MIA and IA in a stage-dependent manner, and the expression was correlated with histologic grade, fluorine-18 fluorodeoxyglucose uptake and poor prognosis. An anti-sense oligonucleotide (ASO) against ARL4C (ARL4C ASO-1316) inhibited RAS-related C3 botulinum toxin substrate activity and nuclear import of Yes-associated protein and transcriptional coactivator with PDZ-binding motif, and suppressed in vitro proliferation and migration of lung cancer cells with KRAS or epidermal growth factor receptor (EGFR) mutations. In addition, transbronchial administration of ARL4C ASO-1316 suppressed orthotopic tumor formation induced by these cancer cells. Thus, ARL4C is involved in the initiation of the premalignant stage and is associated with the stepwise continuum of lung adenocarcinoma. ARL4C ASO-1316 would be useful for lung adenocarcinoma patients expressing ARL4C regardless of the KRAS or EGFR mutation.
(キーワード): A549 Cells / ADP-Ribosylation Factors / Adenocarcinoma / Adenocarcinoma of Lung / Aged / Animals / Cell Movement / Cell Proliferation / Disease Progression / Epithelial Cells / Female / Humans / Hyperplasia / Lung Neoplasms / Male / Mice / Mice, Inbred BALB C / Mice, Nude / Precancerous Conditions / Transcriptional Activation
(出版サイトへのリンク): ● Publication site (DOI): 10.1111/cas.14303
(文献検索サイトへのリンク): ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 31925985; ● Search Scopus @ Elsevier (PMID): 31925985; ● Search Scopus @ Elsevier (DOI): 10.1111/cas.14303

(DOI: 10.1111/cas.14303, PubMed: 31925985) Shinji Matsumoto, Taku Yamamichi, Koei Shinzawa, Yuuya Kasahara, Satoshi Nojima, Takahiro Kodama, Satoshi Obika, Tetsuo Takehara, Eiichi Morii, Hiroomi Okuyama and Akira Kikuchi :
GREB1 induced by Wnt signaling promotes development of hepatoblastoma by suppressing TGFβ signaling.,
Nature Communications, Vol.10, No.1, 3882, 2019.

(要約): The β-catenin mutation is frequently observed in hepatoblastoma (HB), but the underlying mechanism by which Wnt/β-catenin signaling induces HB tumor formation is unknown. Here we show that expression of growth regulation by estrogen in breast cancer 1 (GREB1) depends on Wnt/β-catenin signaling in HB patients. GREB1 is localized to the nucleus where it binds Smad2/3 in a competitive manner with p300 and inhibits TGFβ signaling, thereby promoting HepG2 HB cell proliferation. Forced expression of β-catenin, YAP, and c-Met induces HB-like mouse liver tumor (BYM mice), with an increase in GREB1 expression and HB markers. Depletion of GREB1 strongly suppresses marker gene expression and HB-like liver tumorigenesis, and instead enhances TGFβ signaling in BYM mice. Furthermore, antisense oligonucleotides for GREB1 suppress the formation of HepG2 cell-induced tumors and HB-like tumors in vivo. We propose that GREB1 is a target molecule of Wnt/β-catenin signaling and required for HB progression.
(キーワード): Adolescent / Animals / Antineoplastic Agents / Carcinogenesis / Cell Line, Tumor / Cell Proliferation / Child / Child, Preschool / Gene Expression Regulation, Neoplastic / Hepatoblastoma / Humans / Infant / Infant, Newborn / Liver Neoplasms / Male / Mice / Mice, Nude / Molecular Targeted Therapy / Neoplasm Proteins / Neoplasm Transplantation / Oligonucleotides, Antisense / Transforming Growth Factor beta / Wnt Signaling Pathway / beta Catenin
(出版サイトへのリンク): ● Publication site (DOI): 10.1038/s41467-019-11533-x
(文献検索サイトへのリンク): ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 31462641; ● Search Scopus @ Elsevier (PMID): 31462641; ● Search Scopus @ Elsevier (DOI): 10.1038/s41467-019-11533-x

(DOI: 10.1038/s41467-019-11533-x, PubMed: 31462641) Shinsuke Fujii, Kengo Nagata, Shinji Matsumoto, Ken-Ichi Kohashi, Akira Kikuchi, Yoshinao Oda, Tamotsu Kiyoshima and Naohisa Wada :
Wnt/β-catenin signaling, which is activated in odontomas, reduces Sema3A expression to regulate odontogenic epithelial cell proliferation and tooth germ development.,
Scientific Reports, Vol.9, No.1, 4257, 2019.

(要約): Odontomas, developmental anomalies of tooth germ, frequently occur in familial adenomatous polyposis patients with activated Wnt/β-catenin signaling. However, roles of Wnt/β-catenin signaling in odontomas or odontogenic cells are unclear. Herein, we investigated β-catenin expression in odontomas and functions of Wnt/β-catenin signaling in tooth germ development. β-catenin frequently accumulated in nucleus and/or cellular cytoplasm of odontogenic epithelial cells in human odontoma specimens, immunohistochemically. Wnt/β-catenin signaling inhibited odontogenic epithelial cell proliferation in both cell line and tooth germ development, while inducing immature epithelial bud formation. We identified Semaphorin 3A (Sema3A) as a downstream molecule of Wnt/β-catenin signaling and showed that Wnt/β-catenin signaling-dependent reduction of Sema3A expression resulted in suppressed odontogenic epithelial cell proliferation. Sema3A expression is required in appropriate epithelial budding morphogenesis. These results suggest that Wnt/β-catenin signaling negatively regulates odontogenic epithelial cell proliferation and tooth germ development through decreased-Sema3A expression, and aberrant activation of Wnt/β-catenin signaling may associate with odontoma formation.
(キーワード): Adolescent / Animals / Cell Line / Cell Proliferation / Child / Child, Preschool / DNA Mutational Analysis / Down-Regulation / Embryo, Mammalian / Epithelial Cells / Gene Knockdown Techniques / Humans / Immunohistochemistry / Mice / Odontogenesis / Odontoma / Primary Cell Culture / RNA, Small Interfering / Semaphorin-3A / Tooth Germ / Wnt Signaling Pathway / Young Adult / beta Catenin
(出版サイトへのリンク): ● Publication site (DOI): 10.1038/s41598-019-39686-1
(文献検索サイトへのリンク): ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 30862786; ● Search Scopus @ Elsevier (PMID): 30862786; ● Search Scopus @ Elsevier (DOI): 10.1038/s41598-019-39686-1

(DOI: 10.1038/s41598-019-39686-1, PubMed: 30862786) Takeshi Harada, Shinji Matsumoto, Suguru Hirota, Hirokazu Kimura, Shinsuke Fujii, Yuuya Kasahara, Hidetoshi Gon, Toshihiko Yoshida, Tomoo Itoh, Naotsugu Haraguchi, Tsunekazu Mizushima, Takehiro Noda, Hidetoshi Eguchi, Satoshi Nojima, Eiichi Morii, Takumi Fukumoto, Satoshi Obika and Akira Kikuchi :
Chemically Modified Antisense Oligonucleotide Against ARL4C Inhibits Primary and Metastatic Liver Tumor Growth.,
Molecular Cancer Therapeutics, Vol.18, No.3, 602-612, 2019.

(要約): mRNA levels and inhibited the activity of AKT in HCC cells, suggesting that the downstream signaling of ARL4C in HCC cells is different from that in lung and colon cancer cells. In addition, subcutaneous injection of ARL4C ASO was effective in reducing the growth of primary HCC and metastatic colorectal cancer in the liver of immunodeficient mice. ARL4C ASO accumulated in cancer cells more efficiently than the surrounding normal cells in the liver and decreased ARL4C expression in the tumor. These results suggest that ARL4C ASO represents a novel targeted nucleic acid medicine for the treatment of primary and metastatic liver cancers.
(キーワード): ADP-Ribosylation Factors / Adult / Animals / Cell Line, Tumor / Cell Proliferation / Gene Expression Regulation, Neoplastic / Humans / Liver / Liver Neoplasms / Mice / Neoplasm Metastasis / Oligonucleotides, Antisense / RNA, Small Interfering
(出版サイトへのリンク): ● Publication site (DOI): 10.1158/1535-7163.MCT-18-0824
(文献検索サイトへのリンク): ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 30647122; ● Search Scopus @ Elsevier (PMID): 30647122; ● Search Scopus @ Elsevier (DOI): 10.1158/1535-7163.MCT-18-0824

(DOI: 10.1158/1535-7163.MCT-18-0824, PubMed: 30647122) Hideki Yamamoto, Daisuke Umeda, Shinji Matsumoto and Akira Kikuchi :
LDL switches the LRP6 internalization route from flotillin dependent to clathrin dependent in hepatic cells.,
Journal of Cell Science, Vol.130, No.20, 3542-3556, 2017.

(要約): Low-density lipoprotein (LDL) receptor-related protein 6 (LRP6) was originally identified as a co-receptor of the Wnt signalling pathway and has been shown to be involved in LDL transport. In polarized hepatocytes, many apical proteins are sorted to the basolateral membrane and then internalized and transported to the apical bile canalicular membrane - a process known as transcytosis. We show that LRP6 is transcytosed to the apical membrane of polarized hepatic HepG2 cells via a flotillin-dependent manner in the absence of LDL. LRP6 formed a complex with Niemann-Pick type C1-like 1 (NPC1L1), which is localized to the bile canalicular membrane of the liver and is involved in cholesterol absorption from the bile. LRP6 was required for apical membrane localization of NPC1L1 in the absence of LDL. Clathrin-dependent LRP6 internalization occurred in the presence of LDL, which resulted in trafficking of LRP6 to the lysosome, thereby reducing apical sorting of LRP6 and NPC1L1. These results suggest that LRP6 endocytosis proceeds by two routes, depending on the presence of LDL, and that LRP6 controls the intracellular destination of NPC1L1 in hepatocytes.
(キーワード): Cell Polarity / Clathrin / Hep G2 Cells / Humans / Lipoproteins, LDL / Low Density Lipoprotein Receptor-Related Protein-6 / Membrane Microdomains / Membrane Proteins / Membrane Transport Proteins / Protein Transport / Transcytosis
(出版サイトへのリンク): ● Publication site (DOI): 10.1242/jcs.202135
(文献検索サイトへのリンク): ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 28821575; ● Search Scopus @ Elsevier (PMID): 28821575; ● Search Scopus @ Elsevier (DOI): 10.1242/jcs.202135

(DOI: 10.1242/jcs.202135, PubMed: 28821575) Shinsuke Fujii, Keiko Shinjo, Shinji Matsumoto, Takeshi Harada, Satoshi Nojima, Sunao Sato, Yu Usami, Satoru Toyosawa, Eiichi Morii, Yutaka Kondo and Akira Kikuchi :
Epigenetic upregulation of ARL4C, due to DNA hypomethylation in the 3'-untranslated region, promotes tumorigenesis of lung squamous cell carcinoma.,
Oncotarget, Vol.7, No.49, 81571-81587, 2016.

(要約): ADP-ribosylation factor (ARF)-like 4c (ARL4C) expression, induced by a combination of Wnt/β-catenin and EGF/Ras signaling, has been demonstrated to form epithelial morphogenesis. ARL4C overexpression, due to Wnt/β-catenin and EGF/Ras signaling alterations, was involved in tumorigenesis. It was also reported that ARL4C expression correlates with DNA hypomethylation in the 3'-untranslated region (UTR) of ARL4C gene during lymphogenesis. The current study was conducted to investigate the expression and functions of ARL4C due to DNA hypomethylation in lung and tongue cancers. Immunohistochemical analyses of tissue specimens obtained from lung and tongue squamous cell carcinoma (SCC) patients revealed that ARL4C is not observed in non-tumor regions, but is strongly expressed at high frequencies in tumor lesions. Although inhibition of Wnt/β-catenin or Ras/MAP kinase signaling did not decrease ARL4C expression in NCI-H520 lung SCC cells, ARL4C DNA was clearly hypomethylated in the 3'-UTR. Ten-eleven translocation methylcytosine dioxygenase (TET) enzyme, which mediates DNA demethylation, was highly expressed in NCI-H520 cells. Knockout of TET family proteins (TET1-3) in NCI-H520 cells reduced 5-hydroxymethylcytosine (5hmC) levels and promoted DNA methylation in the 3'-UTR, leading to the decrease in ARL4C expression and ARL4C-mediated cellular migration. In tumor lesions of ARL4C-positive lung SCC, 5hmC was frequently detected and DNA methylation in the 3'-UTR of ARL4C gene was lower than in non-tumor regions, which were consistent with the Cancer Genome Atlas dataset. These results suggest that ARL4C is expressed due to hypomethylation in the 3'-UTR for certain types of cancers and that ARL4C methylation status is involved in cancer cell function.
(キーワード): 3' Untranslated Regions / 5-Methylcytosine / A549 Cells / ADP-Ribosylation Factors / Adult / Aged / Aged, 80 and over / Carcinoma, Squamous Cell / Cell Movement / Cell Proliferation / DNA Methylation / DNA-Binding Proteins / Dioxygenases / Epigenesis, Genetic / Female / Gene Expression Regulation, Neoplastic / HeLa Cells / Head and Neck Neoplasms / Humans / Lung Neoplasms / Male / Middle Aged / Mixed Function Oxygenases / Neoplasm Invasiveness / Proto-Oncogene Proteins / RNA Interference / Signal Transduction / Squamous Cell Carcinoma of Head and Neck / Time Factors / Tongue Neoplasms / Transfection / Up-Regulation
(出版サイトへのリンク): ● Publication site (DOI): 10.18632/oncotarget.13147
(文献検索サイトへのリンク): ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 27835592; ● Search Scopus @ Elsevier (PMID): 27835592; ● Search Scopus @ Elsevier (DOI): 10.18632/oncotarget.13147

(DOI: 10.18632/oncotarget.13147, PubMed: 27835592) Cheng Boon Lim, Shinji Matsumoto, Hideki Yamamoto, Hiroki Mizuno, Junichi Kikuta, Masaru Ishii and Akira Kikuchi :
Prickle1 promotes focal adhesion disassembly in cooperation with the CLASP-LL5β complex in migrating cells.,
Journal of Cell Science, Vol.129, No.16, 3115-3129, 2016.

(要約): Prickle is known to be involved in planar cell polarity, including convergent extension and cell migration; however, the detailed mechanism by which Prickle regulates cellular functions is not well understood. Here, we show that Prickle1 regulates front-rear polarization and migration of gastric cancer MKN1 cells. Prickle1 preferentially accumulated at the cell retraction site in close proximity to paxillin at focal adhesions. Prickle1 dynamics correlated with those of paxillin during focal adhesion disassembly. Furthermore, Prickle1 was required for focal adhesion disassembly. CLASPs (of which there are two isoforms, CLASP1 and CLASP2, in mammals) and LL5β (also known as PHLDB2) have been reported to form a complex at cell edges and to control microtubule-dependent focal adhesion disassembly. Prickle1 was associated with CLASPs and LL5β, and was required for the LL5β-dependent accumulation of CLASPs at the cell edge. Knockdown of CLASPs and LL5β suppressed Prickle1-dependent cell polarization and migration. Prickle1 localized to the membrane through its farnesyl moiety, and the membrane localization was necessary for Prickle1 to regulate migration, to bind to CLASPs and LL5β, and to promote microtubule targeting of focal adhesions. Taken together, these results suggest that Prickle1 promotes focal adhesion disassembly during the retraction processes of cell polarization and migration.
(キーワード): Animals / Carrier Proteins / Cell Line, Tumor / Cell Membrane / Cell Movement / Cell Polarity / Epidermal Growth Factor / Focal Adhesions / HEK293 Cells / Humans / LIM Domain Proteins / Mice / Microtubule-Associated Proteins / Microtubules / Protein Transport / Signal Transduction / Tumor Suppressor Proteins
(出版サイトへのリンク): ● Publication site (DOI): 10.1242/jcs.185439
(文献検索サイトへのリンク): ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 27378169; ● Search Scopus @ Elsevier (PMID): 27378169; ● Search Scopus @ Elsevier (DOI): 10.1242/jcs.185439

(DOI: 10.1242/jcs.185439, PubMed: 27378169) Shinji Matsumoto, Takayuki Kurimoto, Mark M Taketo, Shinsuke Fujii and Akira Kikuchi :
The WNT/MYB pathway suppresses KIT expression to control the timing of salivary proacinar differentiation and duct formation.,
Development, Vol.143, No.13, 2311-2324, 2016.

(要約): Growth factor signaling is involved in the development of various organs, but how signaling regulates organ morphogenesis and differentiation in a coordinated manner remains to be clarified. Here, we show how WNT signaling controls epithelial morphogenetic changes and differentiation using the salivary gland as a model. Experiments using genetically manipulated mice and organ cultures revealed that WNT signaling at an early stage (E12-E15) of submandibular salivary gland (SMG) development inhibits end bud morphogenesis and differentiation into proacini by suppressing Kit expression through the upregulation of the transcription factor MYB, and concomitantly increasing the expression of distal progenitor markers. In addition, WNT signaling at the early stage of SMG development promoted end bud cell proliferation, leading to duct formation. WNT signaling reduction at a late stage (E16-E18) of SMG development promoted end bud maturation and suppressed duct formation. Thus, WNT signaling controls the timing of SMG organogenesis by keeping end bud cells in an undifferentiated bipotent state.
(キーワード): Acinar Cells / Animals / Cell Differentiation / Cell Proliferation / Epithelium / Fibroblast Growth Factors / Mice / Phosphatidylinositol 3-Kinases / Proto-Oncogene Proteins c-akt / Proto-Oncogene Proteins c-kit / Proto-Oncogene Proteins c-myb / Submandibular Gland / Time Factors / Wnt Signaling Pathway
(出版サイトへのリンク): ● Publication site (DOI): 10.1242/dev.134486
(文献検索サイトへのリンク): ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 27161149; ● Search Scopus @ Elsevier (PMID): 27161149; ● Search Scopus @ Elsevier (DOI): 10.1242/dev.134486

(DOI: 10.1242/dev.134486, PubMed: 27161149) Akira Sato, Hisako Kayama, Kensaku Shojima, Shinji Matsumoto, Hirofumi Koyama, Yasuhiro Minami, Satoshi Nojima, Eiichi Morii, Hiroaki Honda, Kiyoshi Takeda and Akira Kikuchi :
The Wnt5a-Ror2 axis promotes the signaling circuit between interleukin-12 and interferon-γ in colitis.,
Scientific Reports, Vol.5, 10536, 2015.

(要約): Wnt5a, which regulates various cellular functions in Wnt signaling, is involved in inflammatory responses, however the mechanism is not well understood. We examined the role of Wnt5a signaling in intestinal immunity using conditional knockout mice for Wnt5a and its receptor Ror2. Removing Wnt5a or Ror2 in adult mice suppressed dextran sodium sulfate (DSS)-induced colitis. It also attenuated the DSS-dependent increase in inflammatory cytokine production and decreased interferon-γ (IFN-γ)-producing CD4(+) Th1 cell numbers in the colon. Wnt5a was highly expressed in stromal fibroblasts in ulcerative lesions in the DSS-treated mice and inflammatory bowel disease patients. Dendritic cells (DCs) isolated from the colon of Wnt5a and Ror2 deficient mice reduced the ability to differentiate naïve CD4(+) T cells to IFN-γ-producing CD4(+) Th1 cells. In vitro experiments demonstrated that the Wnt5a-Ror2 signaling axis augmented the DCs priming effect of IFN-γ, leading to enhanced lipopolysaccharide (LPS)-induced interleukin (IL)-12 expression. Taken together, these results suggest that Wnt5a promotes IFN-γ signaling, leading to IL-12 expression in DCs, and thereby inducing Th1 differentiation in colitis.
(キーワード): Animals / Bone Marrow / Colitis / Cytokines / Dendritic Cells / Dextran Sulfate / Disease Models, Animal / Disease Susceptibility / Fibroblasts / Gene Expression / Inflammation Mediators / Interferon-gamma / Interleukin-12 / Intestinal Mucosa / Mice / Mice, Knockout / Organ Specificity / RNA, Messenger / Receptor Tyrosine Kinase-like Orphan Receptors / Signal Transduction / Wnt Proteins / Wnt-5a Protein
(出版サイトへのリンク): ● Publication site (DOI): 10.1038/srep10536
(文献検索サイトへのリンク): ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 26030277; ● Search Scopus @ Elsevier (PMID): 26030277; ● Search Scopus @ Elsevier (DOI): 10.1038/srep10536

(DOI: 10.1038/srep10536, PubMed: 26030277) Souji Ibuka, Shinji Matsumoto, Shinsuke Fujii and Akira Kikuchi :
The P2Y₂ receptor promotes Wnt3a- and EGF-induced epithelial tubular formation by IEC6 cells by binding to integrins.,
Journal of Cell Science, Vol.128, No.11, 2156-2168, 2015.

(要約): Epithelial tubular structures are essential units in various organs. Here, we used rat intestinal epithelial IEC6 cells to investigate tubulogenesis and we found that tubular formation was induced by a combination of Wnt3a and EGF signaling during three-dimensional culture. Wnt3a and EGF induced the expression of the P2Y2 receptor (P2Y2R, also known as P2RY2), and knockdown of P2Y2R suppressed tubular formation. A P2Y2R mutant that lacks nucleotide responsiveness rescued the phenotypes resulting from P2Y2R knockdown, suggesting that nucleotide-dependent responses are not required for P2Y2R functions in tubular formation. The Arg-Gly-Asp (RGD) sequence of P2Y2R has been shown to interact with integrins, and a P2Y2R mutant lacking integrin-binding activity was unable to induce tubular formation. P2Y2R expression inhibited the interaction between integrins and fibronectin, and induced cell morphological changes and proliferation. Inhibition of integrin and fibronectin binding by treatment with the cyclic RGD peptide and fibronectin knockdown induced tubular formation in the presence of EGF alone, but a fibronectin coat suppressed Wnt3a- and EGF-induced tubular formation. These results suggest that Wnt3a- and EGF-induced P2Y2R expression causes tubular formation by preventing the binding of integrins and fibronectin rather than by mediating nucleotide responses.
(キーワード): Animals / Cell Line / Cell Proliferation / Epidermal Growth Factor / Epithelial Cells / Fibronectins / HEK293 Cells / Humans / Integrins / Morphogenesis / Nucleotides / Rats / Receptors, Purinergic P2Y2 / Signal Transduction / Wnt3A Protein
(出版サイトへのリンク): ● Publication site (DOI): 10.1242/jcs.169060
(文献検索サイトへのリンク): ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 25908848; ● Search Scopus @ Elsevier (PMID): 25908848; ● Search Scopus @ Elsevier (DOI): 10.1242/jcs.169060

(DOI: 10.1242/jcs.169060, PubMed: 25908848) Hideki Yamamoto, Chihiro Awada, Shinji Matsumoto, Tomoyuki Kaneiwa, Takayuki Sugimoto, Toshifumi Takao and Akira Kikuchi :
Basolateral secretion of Wnt5a in polarized epithelial cells is required for apical lumen formation.,
Journal of Cell Science, Vol.128, No.5, 1051-1063, 2015.

(要約): Wnt5a regulates planar cell polarity in epithelial cells, but it remains to be determined whether Wnt5a and its receptors are sorted apically or basolaterally, and how Wnt5a signaling is involved in apical and basolateral polarization. We found that Wnt5a was secreted basolaterally in polarized kidney epithelial cells. The basolateral secretion of Wnt5a required Wntless (Wls), clathrin and adaptor protein 1 (AP-1). Wnt5a receptors were also localized to the basolateral membranes, but their sorting did not require Wls. Wnt5a-induced signaling was stimulated more efficiently at the basolateral side than the apical side of epithelial cells. Knockdown of Wnt5a delayed apical lumen formation of the epithelial cyst, and these phenotypes were rescued by wild-type Wnt5a, but not by a Wnt5a mutant that is secreted apically. Although apoptosis was not required for apical lumen formation in a wild-type cyst, apoptosis was necessary for eliminating luminal cells in a Wnt5a-depleted cyst. These results suggest that Wnt5a and its receptors are sorted to their correct destination by different mechanisms and that the basolateral secretion of Wnt5a is necessary for apical lumen formation in the epithelial cyst.
(キーワード): Animals / Apoptosis / Cell Polarity / Cysts / Dogs / Epithelial Cells / Madin Darby Canine Kidney Cells / Mice / Mutation / NIH 3T3 Cells / Rats / Wnt Proteins / Wnt-5a Protein
(出版サイトへのリンク): ● Publication site (DOI): 10.1242/jcs.163683
(文献検索サイトへのリンク): ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 25593127; ● Search Scopus @ Elsevier (PMID): 25593127; ● Search Scopus @ Elsevier (DOI): 10.1242/jcs.163683

(DOI: 10.1242/jcs.163683, PubMed: 25593127) Shinsuke Fujii, Shinji Matsumoto, Satoshi Nojima, Eiichi Morii and Akira Kikuchi :
Arl4c expression in colorectal and lung cancers promotes tumorigenesis and may represent a novel therapeutic target.,
Oncogene, Vol.34, No.37, 4834-4844, 2014.

(要約): We recently demonstrated that expression of ADP-ribosylation factor (ARF)-like 4c (Arl4c) induced by a combination of Wnt/β-catenin and epidermal growth factor/Ras signaling in normal epithelial cells grown in three-dimensional culture promotes cellular migration and proliferation, resulting in formation of tube-like structures, suggesting the involvement of Arl4c in epithelial morphogenesis. It is conceivable that there could be a common mechanism between epithelial morphogenesis and carcinogenesis. Therefore the current study was conducted to investigate whether Arl4c might be involved in tumorigenesis. Immunohistochemical analyses of tissue specimens obtained from colorectal and lung cancer patients revealed that Arl4c was not observed in non-tumor regions but was strongly expressed at high frequencies in tumor lesions. Inhibition of Wnt/β-catenin or Ras/mitogen-activated protein kinase signaling reduced Arl4c mRNA levels in HCT116 colorectal cancer cells and A549 lung cancer cells. Knockdown of Arl4c inhibited Rac activity and also prevented nuclear localization of yes-associated protein (YAP)/transcriptional co-activator with PDZ-binding motif (TAZ) in these cancer cells. Arl4c-depleted cancer cells consistently showed decreased migration, invasion and proliferation capabilities both in vitro and in vivo. Furthermore, direct injection of Arl4c small interfering RNA (siRNA) into HCT116 cell-derived tumors (in vivo treatment with siRNA) inhibited tumor growth in immunodeficient mice. These results suggest that Arl4c is involved in tumorigenesis and might represent a novel therapeutic target for suppressing proliferation and invasion of colorectal and lung cancer cells.
(キーワード): ADP-Ribosylation Factors / Adenocarcinoma / Adult / Aged / Aged, 80 and over / Animals / Cell Transformation, Neoplastic / Colorectal Neoplasms / Gene Expression Regulation, Neoplastic / HCT116 Cells / HEK293 Cells / HeLa Cells / Humans / Lung Neoplasms / Male / Mice / Mice, Inbred BALB C / Mice, Nude / Middle Aged / Molecular Targeted Therapy / RNA, Small Interfering / Tumor Cells, Cultured / Xenograft Model Antitumor Assays
(出版サイトへのリンク): ● Publication site (DOI): 10.1038/onc.2014.402
(文献検索サイトへのリンク): ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 25486429; ● Search Scopus @ Elsevier (PMID): 25486429; ● Search Scopus @ Elsevier (DOI): 10.1038/onc.2014.402

(DOI: 10.1038/onc.2014.402, PubMed: 25486429) Shinji Matsumoto, Shinsuke Fujii, Akira Sato, Souji Ibuka, Yoshinori Kagawa, Masaru Ishii and Akira Kikuchi :
A combination of Wnt and growth factor signaling induces Arl4c expression to form epithelial tubular structures.,
The EMBO Journal, Vol.33, No.7, 702-718, 2014.

(要約): Growth factor-dependent epithelial morphological changes and proliferation are essential for the formation of tubular structures, but the underlying molecular mechanisms are poorly understood. Co-stimulation with Wnt3a and epidermal growth factor (Wnt3a/EGF) induced development of tubes consisting of intestinal epithelial cells by inducing expression of Arl4c, an Arf-like small GTP-binding protein, in three-dimensional culture, while stimulation with Wnt3a or EGF alone did not. Arl4c expression resulted in rearrangement of the cytoskeleton through activation of Rac and inactivation of Rho properly, which promoted cell growth by inducing nuclear translocation of Yes-associated protein and transcriptional co-activator with PDZ-binding motif (YAP/TAZ) in leading cells. Arl4c was expressed in ureteric bud tips and pretubular structures in the embryonic kidney. In an organoid culture assay, Wnt and fibroblast growth factor signaling simultaneously induced elongation and budding of kidney ureteric buds through Arl4c expression. YAP/TAZ was observed in the nucleus of extending ureteric bud tips. Thus, Arl4c expression induced by a combination of growth factor signaling mechanisms is involved in tube formation.
(キーワード): ADP-Ribosylation Factors / Acyltransferases / Animals / Cell Adhesion / Cell Differentiation / Cells, Cultured / Cytoskeleton / Dogs / Epidermal Growth Factor / Epithelial Cells / Female / Fetus / Fibroblast Growth Factors / HeLa Cells / Humans / Intestinal Mucosa / Intestines / Kidney / Madin Darby Canine Kidney Cells / Mice / Mice, Inbred C57BL / Rats / Signal Transduction / Transcription Factors / Wnt3 Protein
(出版サイトへのリンク): ● Publication site (DOI): 10.1002/embj.201386942
(文献検索サイトへのリンク): ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 24562386; ● Search Scopus @ Elsevier (PMID): 24562386; ● Search Scopus @ Elsevier (DOI): 10.1002/embj.201386942

(DOI: 10.1002/embj.201386942, PubMed: 24562386) Yoshinori Kagawa, Shinji Matsumoto, Yuji Kamioka, Koshi Mimori, Yoko Naito, Taeko Ishii, Daisuke Okuzaki, Naohiro Nishida, Sakae Maeda, Atsushi Naito, Junichi Kikuta, Keizo Nishikawa, Junichi Nishimura, Naotsugu Haraguchi, Ichiro Takemasa, Tsunekazu Mizushima, Masataka Ikeda, Hirofumi Yamamoto, Mitsugu Sekimoto, Hideshi Ishii, Yuichiro Doki, Michiyuki Matsuda, Akira Kikuchi, Masaki Mori and Masaru Ishii :
Cell cycle-dependent Rho GTPase activity dynamically regulates cancer cell motility and invasion in vivo.,
PLoS ONE, Vol.8, No.12, e83629, 2013.

(要約): The mechanism behind the spatiotemporal control of cancer cell dynamics and its possible association with cell proliferation has not been well established. By exploiting the intravital imaging technique, we found that cancer cell motility and invasive properties were closely associated with the cell cycle. In vivo inoculation of human colon cancer cells bearing fluorescence ubiquitination-based cell cycle indicator (Fucci) demonstrated an unexpected phenomenon: S/G2/M cells were more motile and invasive than G1 cells. Microarray analyses showed that Arhgap11a, an uncharacterized Rho GTPase-activating protein (RhoGAP), was expressed in a cell-cycle-dependent fashion. Expression of ARHGAP11A in cancer cells suppressed RhoA-dependent mechanisms, such as stress fiber formation and focal adhesion, which made the cells more prone to migrate. We also demonstrated that RhoA suppression by ARHGAP11A induced augmentation of relative Rac1 activity, leading to an increase in the invasive properties. RNAi-based inhibition of Arhgap11a reduced the invasion and in vivo expansion of cancers. Additionally, analysis of human specimens showed the significant up-regulation of Arhgap11a in colon cancers, which was correlated with clinical invasion status. The present study suggests that ARHGAP11A, a cell cycle-dependent RhoGAP, is a critical regulator of cancer cell mobility and is thus a promising therapeutic target in invasive cancers.
(キーワード): Cell Cycle / Cell Line, Tumor / Cell Movement / Colorectal Neoplasms / Enzyme Activation / GTPase-Activating Proteins / Gene Expression / Gene Knockdown Techniques / HCT116 Cells / Humans / Neoplasm Invasiveness / Neoplasms
(出版サイトへのリンク): ● Publication site (DOI): 10.1371/journal.pone.0083629
(文献検索サイトへのリンク): ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 24386239; ● Search Scopus @ Elsevier (PMID): 24386239; ● Search Scopus @ Elsevier (DOI): 10.1371/journal.pone.0083629

(DOI: 10.1371/journal.pone.0083629, PubMed: 24386239) Hidetoshi Gon, Katsumi Fumoto, Yonson Ku, Shinji Matsumoto and Akira Kikuchi :
Wnt5a signaling promotes apical and basolateral polarization of single epithelial cells.,
Molecular Biology of the Cell, Vol.24, No.23, 3764-3774, 2013.

(要約): Single epithelial-derived tumor cells have been shown to induce apical and basolateral (AB) polarity by expression of polarization-related proteins. However, physiological cues and molecular mechanisms for AB polarization of single normal epithelial cells are unclear. When intestinal epithelial cells 6 (IEC6 cells) were seeded on basement membrane proteins (Matrigel), single cells formed an F-actin cap on the upper cell surface, where apical markers accumulated, and a basolateral marker was localized to the rest of the cell surface region, in a Wnt5a signaling-dependent manner. However, these phenotypes were not induced by type I collagen. Rac1 activity in the noncap region was higher than that in the cap region, whereas Rho activity increased toward the cap region. Wnt5a signaling activated and inhibited Rac1 and RhoA, respectively, independently through Tiam1 and p190RhoGAP-A, which formed a tertiary complex with Dishevelled. Furthermore, Wnt5a signaling through Rac1 and RhoA was required for cystogenesis of IEC6 cells. These results suggest that Wnt5a promotes the AB polarization of IEC6 cells through regulation of Rac and Rho activities in a manner dependent on adhesion to specific extracellular matrix proteins.
(キーワード): Adaptor Proteins, Signal Transducing / Animals / Cell Polarity / Cell Shape / Chlorocebus aethiops / Collagen / Dishevelled Proteins / Drug Combinations / Enterocytes / Epithelial Cells / Green Fluorescent Proteins / Guanine Nucleotide Exchange Factors / HEK293 Cells / HeLa Cells / Humans / Laminin / Microvilli / Neoplasm Proteins / Phosphoproteins / Protein Transport / Proteoglycans / Rats / Repressor Proteins / Signal Transduction / T-Lymphoma Invasion and Metastasis-inducing Protein 1 / Vero Cells / Wnt Proteins / Wnt-5a Protein / rac1 GTP-Binding Protein / rho GTP-Binding Proteins
(出版サイトへのリンク): ● Publication site (DOI): 10.1091/mbc.E13-07-0357
(文献検索サイトへのリンク): ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 24088568; ● Search Scopus @ Elsevier (PMID): 24088568; ● Search Scopus @ Elsevier (DOI): 10.1091/mbc.E13-07-0357

(DOI: 10.1091/mbc.E13-07-0357, PubMed: 24088568) Maki Ishida-Takagishi, Atsushi Enomoto, Naoya Asai, Kaori Ushida, Takashi Watanabe, Takahiko Hashimoto, Takuya Kato, Liang Weng, Shinji Matsumoto, Masato Asai, Yoshiki Murakumo, Kozo Kaibuchi, Akira Kikuchi and Masahide Takahashi :
The Dishevelled-associating protein Daple controls the non-canonical Wnt/Rac pathway and cell motility.,
Nature Communications, Vol.3, 859, 2012.

(要約): Dishevelled is the common mediator of canonical and non-canonical Wnt signalling pathways, which are important for embryonic development, tissue maintenance and cancer progression. In the non-canonical Wnt signalling pathway, the Rho family of small GTPases acting downstream of Dishevelled has essential roles in cell migration. The mechanisms by which the non-canonical Wnt signalling pathway regulates Rac activation remain unknown. Here we show that Daple (Dishevelled-associating protein with a high frequency of leucine residues) regulates Wnt5a-mediated activation of Rac and formation of lamellipodia through interaction with Dishevelled. Daple increases the association of Dishevelled with an isoform of atypical protein kinase C, consequently promoting Rac activation. Accordingly, Daple deficiency impairs migration of fibroblasts and epithelial cells during wound healing in vivo. These findings indicate that Daple interacts with Dishevelled to direct the Dishevelled/protein kinase λ protein complex to activate Rac, which in turn mediates the non-canonical Wnt signalling pathway required for cell migration.
(キーワード): Adaptor Proteins, Signal Transducing / Animals / Blotting, Western / Carrier Proteins / Cell Line / Cell Movement / Cells, Cultured / Dishevelled Proteins / Fibroblasts / Humans / Immunohistochemistry / Immunoprecipitation / Keratinocytes / Mice / Mice, Knockout / Models, Biological / Phosphoproteins / Protein Binding / Protein Kinase C / Signal Transduction / Wnt Proteins / Wnt-5a Protein
(出版サイトへのリンク): ● Publication site (DOI): 10.1038/ncomms1861
(文献検索サイトへのリンク): ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 22643886; ● Search Scopus @ Elsevier (PMID): 22643886; ● Search Scopus @ Elsevier (DOI): 10.1038/ncomms1861

(DOI: 10.1038/ncomms1861, PubMed: 22643886) Hiroshi Sakane, Hideki Yamamoto, Shinji Matsumoto, Akira Sato and Akira Kikuchi :
Localization of glypican-4 in different membrane microdomains is involved in the regulation of Wnt signaling.,
Journal of Cell Science, Vol.125, No.Pt 2, 449-460, 2012.

(要約): Glypicans are members of the heparan sulfate proteoglycans (HSPGs) and are involved in various growth factor signaling mechanisms. Although HSPGs affect the β-catenin-dependent and -independent pathways of Wnt signaling, how they regulate distinct Wnt pathways is not clear. It has been suggested that the β-catenin-dependent pathway is initiated through receptor endocytosis in lipid raft microdomains and the independent pathway is activated through receptor endocytosis in non-lipid raft microdomains. Here, evidence is presented that glypican-4 (GPC4) is localized to both membrane microdomains and that the localization affects its ability to regulate distinct Wnt pathways. GPC4 bound to Wnt3a and Wnt5a, which activate the β-catenin-dependent and -independent pathways, respectively, and colocalized with Wnts on the cell surface. LRP6, one of Wnt3a coreceptors, was present in lipid raft microdomains, whereas Ror2, one of Wnt5a coreceptors, was localized to non-lipid raft microdomains. Expression of GPC4 enhanced the Wnt3a-dependent β-catenin pathway and the Wnt5a-dependent β-catenin-independent pathway, and knockdown of GPC4 suppressed both pathways. A GPC4 mutant that was localized to only non-lipid raft microdomains inhibited the β-catenin-dependent pathway but enhanced the β-catenin-independent pathway. These results suggest that GPC4 concentrates Wnt3a and Wnt5a to the vicinity of their specific receptors in different membrane microdomains, thereby regulating distinct Wnt signaling.
(キーワード): Cell Line / ErbB Receptors / Glypicans / Humans / Intercellular Signaling Peptides and Proteins / Membrane Microdomains / Protein Structure, Tertiary / Receptors, Wnt / Recombinant Fusion Proteins / Syndecan-1 / Wnt Proteins / Wnt Signaling Pathway / Wnt3A Protein / beta Catenin
(出版サイトへのリンク): ● Publication site (DOI): 10.1242/jcs.091876
(文献検索サイトへのリンク): ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 22302992; ● Search Scopus @ Elsevier (PMID): 22302992; ● Search Scopus @ Elsevier (DOI): 10.1242/jcs.091876

(DOI: 10.1242/jcs.091876, PubMed: 22302992) Shinji Matsumoto and Akira Kikuchi :
Regulation of focal adhesion dynamics by Wnt5a signaling.,
Methods in Molecular Biology, Vol.839, 215-227, 2012.

(要約): Wnt5a is a representative ligand that activates the β-catenin-independent pathway of Wnt signaling in mammals. This pathway might be related to planar cell polarity signaling in Drosophila. Because reliable biochemical assays to measure Wnt5a pathway activity have not yet been established, we examined whether Wnt5a signaling stimulates focal adhesion turnover in migrating cells using live immunofluorescence imaging and immunocytochemical analysis. These assays demonstrated that the Wnt5a pathway cooperates with integrin signaling to regulate cell migration and adhesion through focal adhesion dynamics.
(キーワード): Animals / Cell Movement / Cell Survival / Chlorocebus aethiops / Focal Adhesions / Frizzled Receptors / Gene Knockdown Techniques / HeLa Cells / Humans / Immunohistochemistry / Integrin beta1 / Intracellular Space / Molecular Imaging / Plasmids / Protein Transport / Proto-Oncogene Proteins / RNA, Small Interfering / Signal Transduction / Transfection / Vero Cells / Wnt Proteins / Wnt-5a Protein
(出版サイトへのリンク): ● Publication site (DOI): 10.1007/978-1-61779-510-7_17
(文献検索サイトへのリンク): ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 22218904; ● Search Scopus @ Elsevier (PMID): 22218904; ● Search Scopus @ Elsevier (DOI): 10.1007/978-1-61779-510-7_17

(DOI: 10.1007/978-1-61779-510-7_17, PubMed: 22218904) Hideaki Hanaki, Hideki Yamamoto, Hiroshi Sakane, Shinji Matsumoto, Hideki Ohdan, Akira Sato and Akira Kikuchi :
An anti-Wnt5a antibody suppresses metastasis of gastric cancer cells in vivo by inhibiting receptor-mediated endocytosis.,
Molecular Cancer Therapeutics, Vol.11, No.2, 298-307, 2011.

(要約): Wnt5a is a representative ligand that activates the β-catenin-independent pathway in Wnt signaling. It was reported that the expression of Wnt5a in human gastric cancer is associated with aggressiveness and poor prognosis and that knockdown of Wnt5a reduces the ability of gastric cancer cells to metastasize in nude mice. Therefore, Wnt5a and its signaling pathway might be important targets for the therapy of gastric cancer. The aim of this study was to examine whether an anti-Wnt5a antibody affects metastasis of gastric cancer cells. One anti-Wnt5a polyclonal antibody (pAb5a-5) inhibited migration and invasion activities in vitro of gastric cancer cells with a high expression level of Wnt5a. Previously, it was shown that Wnt5a induces the internalization of receptors, which is required for Wnt5a-dependent activation of Rac1. pAb5a-5 inhibited Wnt5a-dependent internalization of receptors, thereby suppressed Wnt5a-dependent activation of Rac1. Laminin γ2 is one of target genes of Wnt5a signaling and Rac1 was involved in its expression. pAb5a-5 also inhibited Wnt5a-dependent expression of laminin γ2. In an experimental liver metastasis assay, gastric cancer cells were introduced into the spleens of nude mice. Laminin γ2 was required for liver metastatic ability of gastric cancer cells in vivo. Furthermore, intraperitoneal injection of pAb5a-5 inhibited the metastatic ability of gastric cancer cells. These results suggest that an anti-Wnt5a antibody was capable of suppressing Wnt5a-dependent internalization of receptors, resulting in the prevention of metastasis of gastric cancer cells by inhibiting the activation of Rac1 and the expression of laminin γ2.
(キーワード): Animals / Antibodies, Monoclonal / Cell Culture Techniques / Cell Line, Tumor / Cell Movement / Endocytosis / Enzyme Activation / Frizzled Receptors / Gene Expression / HEK293 Cells / Humans / Immunoblotting / Laminin / Liver Neoplasms / Male / Mice / Mice, Inbred BALB C / Mice, Nude / Proto-Oncogene Proteins / RNA Interference / Reverse Transcriptase Polymerase Chain Reaction / Stomach Neoplasms / Wnt Proteins / Wnt-5a Protein / Xenograft Model Antitumor Assays / rac1 GTP-Binding Protein
(出版サイトへのリンク): ● Publication site (DOI): 10.1158/1535-7163.MCT-11-0682
(文献検索サイトへのリンク): ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 22101459; ● Search Scopus @ Elsevier (PMID): 22101459; ● Search Scopus @ Elsevier (DOI): 10.1158/1535-7163.MCT-11-0682

(DOI: 10.1158/1535-7163.MCT-11-0682, PubMed: 22101459) Shinji Matsumoto, Katsumi Fumoto, Tetsuji Okamoto, Kozo Kaibuchi and Akira Kikuchi :
Binding of APC and dishevelled mediates Wnt5a-regulated focal adhesion dynamics in migrating cells.,
The EMBO Journal, Vol.29, No.7, 1192-1204, 2010.

(要約): Wnt5a is a representative ligand that activates the Wnt/beta-catenin-independent pathway, resulting in the regulation of cell adhesion, migration, and polarity, but its molecular mechanism is poorly understood. This report shows that Dishevelled (Dvl) binds to adenomatous polyposis coli (APC) gene product, and this binding is enhanced by Wnt5a. Dvl was involved in the stabilization of the plus end dynamics of microtubules as well as APC. Frizzled2 (Fz2) was present with Wnt5a at the leading edge of migrating cells and formed a complex with APC through Dvl. Fz2 also interacted with integrins at the leading edge, and Dvl and APC associated with and activated focal adhesion kinase and paxillin. The binding of APC to Dvl enhanced the localization of paxillin to the leading edge and was involved in Wnt5a-dependent focal adhesion turnover. Furthermore, this new Wnt5a signalling pathway was important for the epithelial morphogenesis in the three-dimensional culture. These results suggest that the functional and physical interaction of Dvl and APC is involved in Wnt5a/Fz2-dependent focal adhesion dynamics during cell migration and epithelial morphogenesis.
(キーワード): Adaptor Proteins, Signal Transducing / Animals / COS Cells / Cell Adhesion / Cell Line / Cell Movement / Chlorocebus aethiops / Dishevelled Proteins / Epithelial Cells / Focal Adhesions / Frizzled Receptors / Genes, APC / HeLa Cells / Humans / Phosphoproteins / Protein Binding / Vero Cells / Wnt Proteins
(出版サイトへのリンク): ● Publication site (DOI): 10.1038/emboj.2010.26
(文献検索サイトへのリンク): ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 20224554; ● Search Scopus @ Elsevier (PMID): 20224554; ● Search Scopus @ Elsevier (DOI): 10.1038/emboj.2010.26

(DOI: 10.1038/emboj.2010.26, PubMed: 20224554) 福井康人, 虎谷茂昭, 小泉浩一, 松本真司, 林堂安貴, 岡本哲治 :
オトガイ部知覚異常を初発症状とした側頭下窩に進展した筋肉内脂肪腫の1例,
日口外誌, Vol.55, No.11, 580-584, 2009年.

(出版サイトへのリンク): ● Publication site (DOI): 10.5794/jjoms.55.580
(文献検索サイトへのリンク): ● CiNii @ 国立情報学研究所 (CRID): 1390001206532866176; ● Search Scopus @ Elsevier (DOI): 10.5794/jjoms.55.580

(DOI: 10.5794/jjoms.55.580, CiNii: 1390001206532866176)

MISC

研究者総覧に該当データはありませんでした。

総説・解説

Shinji Matsumoto and Akira Kikuchi :
Wnt/β-catenin signaling pathway in liver biology and tumorigenesis.,
In Vitro Cellular & Developmental Biology. Animal, Vol.60, No.5, 466-481, Feb. 2024.

(要約): The Wnt/β-catenin pathway is an evolutionarily conserved signaling pathway that controls fundamental physiological and pathological processes by regulating cell proliferation and differentiation. The Wnt/β-catenin pathway enables liver homeostasis by inducing differentiation and contributes to liver-specific features such as metabolic zonation and regeneration. In contrast, abnormalities in the Wnt/β-catenin pathway promote the development and progression of hepatocellular carcinoma (HCC). Similarly, hepatoblastoma, the most common childhood liver cancer, is frequently associated with β-catenin mutations, which activate Wnt/β-catenin signaling. HCCs with activation of the Wnt/β-catenin pathway have unique gene expression patterns and pathological and clinical features. Accordingly, they are highly differentiated with retaining hepatocyte-like characteristics and tumorigenic. Activation of the Wnt/β-catenin pathway in HCC also alters the state of immune cells, causing "immune evasion" with inducing resistance to immune checkpoint inhibitors, which have recently become widely used to treat HCC. Activated Wnt/β-catenin signaling exhibits these phenomena in liver tumorigenesis through the expression of downstream target genes, and the molecular basis is still poorly understood. In this review, we describe the physiological roles of Wnt/b-catenin signaling and then discuss their characteristic changes by the abnormal activation of Wnt/b-catenin signaling. Clarification of the mechanism would contribute to the development of therapeutic agents in the future.
(キーワード): Humans / Wnt Signaling Pathway / Carcinogenesis / Liver Neoplasms / Animals / Liver / Carcinoma, Hepatocellular / beta Catenin
(出版サイトへのリンク): ● Publication site (DOI): 10.1007/s11626-024-00858-7
(文献検索サイトへのリンク): ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 38379098; ● Search Scopus @ Elsevier (PMID): 38379098; ● Search Scopus @ Elsevier (DOI): 10.1007/s11626-024-00858-7

(DOI: 10.1007/s11626-024-00858-7, PubMed: 38379098) 松本真司 :
【核酸医薬が飛躍する時】肝がんに対する核酸医薬品の開発動向,
Medical Science Digest, Vol.49, No.14, 744-747, 2023年12月.

(要約): 肝がんは世界的に死亡率の高い難治性のがんであり,進行がんに対する既存の治療法は有効性が限定的である．アンチセンスやsiRNAなどの核酸医薬は,肝がんの発生や進行に関与する多様なシグナル経路を標的とすることができるため,有望なモダリティとして注目されている．核酸修飾技術や薬物送達技術の進歩により,いくつかの核酸医薬は前臨床研究や臨床試験で抗腫瘍効果や安全性が示されている．今後,さらなる研究開発によって,核酸医薬が肝がんの治療薬として治療成績の向上に貢献することが期待される．(著者抄録)

Akira Kikuchi, Shinji Matsumoto and Ryota Sada :
Dickkopf signaling, beyond Wnt-mediated biology.,
Seminars in Cell & Developmental Biology, Vol.125, 55-65, Nov. 2021.

(要約): Dickkopf1 (DKK1) was originally identified as a secreted protein that antagonizes Wnt signaling. Although DKK1 is essential for the developmental process, its functions in postnatal and adult life are unclear. However, evidence is accumulating that DKK1 is involved in tumorigenesis in a manner unrelated to Wnt signaling. In addition, recent studies have revealed that DKK1 may control immune reactions, although the relationship of this to Wnt signaling is unknown. Other DKK family members, DKK2-4, are likely to have their own functions. Here, we review the possible novel functions of DKKs. We summarize the characteristics of receptors of DKKs and the signaling mechanisms through DKKs and their receptors, provide evidence showing that DKKs are involved in tumor aggressiveness independently of Wnt signaling, and emphasize promising cancer therapies targeting DKKs and receptors. Lastly, we discuss various physiological and pathological processes controlled by DKKs.
(キーワード): Adult / Biology / Humans / Intercellular Signaling Peptides and Proteins / Neoplasms / Wnt Signaling Pathway
(出版サイトへのリンク): ● Publication site (DOI): 10.1016/j.semcdb.2021.11.003
(文献検索サイトへのリンク): ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 34801396; ● Search Scopus @ Elsevier (PMID): 34801396; ● Search Scopus @ Elsevier (DOI): 10.1016/j.semcdb.2021.11.003

(DOI: 10.1016/j.semcdb.2021.11.003, PubMed: 34801396) 松本真司 :
上皮管腔形態形成の分子機構とその異常による腫瘍形成,
生化学, Vol.93, No.5, 733-748, 2021年10月.

(出版サイトへのリンク): ● Publication site (DOI): 10.14952/seikagaku.2021.930733
(文献検索サイトへのリンク): ● CiNii @ 国立情報学研究所 (CRID): 1390852870557767680; ● Search Scopus @ Elsevier (DOI): 10.14952/seikagaku.2021.930733

(DOI: 10.14952/seikagaku.2021.930733, CiNii: 1390852870557767680) 山道拓, 松本真司, 奥山宏臣, 菊池章 :
肝芽腫におけるWntシグナル関連新規創薬標的GREB1の同定と核酸医薬の開発,
日本小児血液・がん学会雑誌, Vol.57, No.2, 116-120, 2020年.

(出版サイトへのリンク): ● Publication site (DOI): 10.11412/jspho.57.116
(文献検索サイトへのリンク): ● CiNii @ 国立情報学研究所 (CRID): 1390567172566092672; ● Search Scopus @ Elsevier (DOI): 10.11412/jspho.57.116

(DOI: 10.11412/jspho.57.116, CiNii: 1390567172566092672) 松本真司, 菊池章 :
Wntシグナルの研究を基盤とした新規の抗がん剤の開発,
領域融合レビュー, Vol.7, e009, 2018年.

(出版サイトへのリンク): ● Publication site (DOI): 10.7875/leading.author.7.e009
(文献検索サイトへのリンク): ● CiNii @ 国立情報学研究所 (CRID): 1390853649183082240; ● Search Scopus @ Elsevier (DOI): 10.7875/leading.author.7.e009

(DOI: 10.7875/leading.author.7.e009, CiNii: 1390853649183082240) Shinji Matsumoto, Shinsuke Fujii and Akira Kikuchi :
Arl4c is a key regulator of tubulogenesis and tumourigenesis as a target gene of Wnt-β-catenin and growth factor-Ras signalling.,
The Journal of Biochemistry, Vol.161, No.1, 27-35, Nov. 2016.

(要約): Epithelial tubular morphogenesis (tubulogenesis) is a fundamental morphogenetic process of many epithelial organs. In this developmental process, epithelial cells migrate, proliferate, polarize and differentiate towards surrounding mesenchymal tissue to form tubule structures. Although epithelial tissue structures are basically stable in the postnatal period, epithelial cells regain highly proliferative and invasive potentials within mesenchymal tissue during tumour formation (tumourigenesis). Therefore, there must be a common molecular basis orchestrating the cellular behaviours involved in both tubulogenesis and tumourigenesis. ADP-ribosylation factor (Arf)-like protein 4c (Arl4c), which belongs to the small GTP-binding protein family, is expressed by the simultaneous activation of Wnt-β-catenin and growth factor-Ras-mitogen-activated protein kinase signalling, was identified as an essential regulator of tubulogenesis. Arl4c expression was also involved in the tumour formation of colorectal and lung cancers. In this review, we focus on Arl4c as a novel Wnt signal target molecule that links epithelial tubulogenesis to tumourigenesis.
(キーワード): ADP-Ribosylation Factors / Animals / Cell Transformation, Neoplastic / Colorectal Neoplasms / Humans / Kidney Tubules / Lung Neoplasms / Oncogene Protein p21(ras) / Wnt Proteins / beta Catenin
(出版サイトへのリンク): ● Publication site (DOI): 10.1093/jb/mvw069
(文献検索サイトへのリンク): ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 28053143; ● Search Scopus @ Elsevier (PMID): 28053143; ● Search Scopus @ Elsevier (DOI): 10.1093/jb/mvw069

(DOI: 10.1093/jb/mvw069, PubMed: 28053143) 松本真司, 菊池章 :
【消化管の再生医療】In vitro実験系を用いた上皮管腔組織形成の分子基盤の確立,
G.I.Research, Vol.22, No.5, 450-456, 2014年10月.

(要約): 生体を構成する呼吸器系，尿路系，外分泌系などの器官は，極性化した上皮細胞から成る管(チューブ)状の上皮管腔組織が基本構成単位となる．上皮管腔組織の形成・維持にはWntをはじめ上皮成長因子(EGF)や線維芽細胞増殖因子(FGF)，骨形成因子(BMP)といった液性因子や，基底膜などの細胞外基質(ECM)からの接着シグナルが必要不可欠である．組織幹細胞の研究が急速に進展している一方で，上皮細胞集団からなる組織・器官の形成と維持の分子・細胞レベルでの理解は大きく立ち遅れている．最近，培養上皮細胞やマウス胎児器官を用いて，WntがEGFなどの増殖因子と協調的に上皮細胞集団の細胞骨格や形態，増殖を制御し，管腔組織形成を誘導する新たな機構が明らかになってきた．これらの上皮管腔組織形成の分子基盤の解明は，消化管形成機構の理解と再生医療への応用に貢献すると期待される．(著者抄録)
(キーワード): 器官培養技術 *上皮上皮細胞 *器官形成細胞培養技術 ADP-Ribosylation Factors 細胞増殖 *Wntシグナル伝達経路 ARL4A Protein マウス動物

松本真司, 菊池章 :
特集細胞接着の制御 Wnt 5aシグナルによる細胞の極性と遊走·接着の制御,
生体の科学, Vol.64, No.3, 226-231, 2013年6月.

(出版サイトへのリンク): ● Publication site (DOI): 10.11477/mf.2425101444
(文献検索サイトへのリンク): ● CiNii @ 国立情報学研究所 (CRID): 1390283684892110848; ● Search Scopus @ Elsevier (DOI): 10.11477/mf.2425101444

(DOI: 10.11477/mf.2425101444, CiNii: 1390283684892110848) 松本真司, 菊池章 :
特集 Wnt協奏曲:新たな活性化機構と他の増殖·分化シグナルとの協調による形態形成 (第2部)Wntシグナルと幹細胞からの組織形態形成 Wntと増殖因子の協調的シグナルによる上皮管腔組織形成,
細胞工学, Vol.32, No.4, 435-441, 2013年3月.

(出版サイトへのリンク): ● Publication site (DOI): 10.15105/j01677.2013172429
(文献検索サイトへのリンク): ● CiNii @ 国立情報学研究所 (CRID): 1390282763103399296; ● Search Scopus @ Elsevier (DOI): 10.15105/j01677.2013172429

(DOI: 10.15105/j01677.2013172429, CiNii: 1390282763103399296) 松本真司, 菊池章, 松本真司 :
【シグナル伝達研究最前線2012 翻訳後修飾，解析技術，疾患との連関から創薬応用まで】(第3章)シグナル伝達の破綻と疾患との連関 Wntシグナルの異常と消化器がん,
実験医学, Vol.30, No.5, 823-830, 2012年3月.

(要約): ショウジョウバエの遺伝学に端を発したWnt研究は，腫瘍医学や発生生物学においても解析が進み，多様な研究領域に展開した．特に腫瘍医学領域では，大腸がんにおけるWntシグナル研究は組織幹細胞マーカーLgr5の発見に貢献した．また，がんの発症，悪性化には慢性炎症の存在が背景となることが示唆され，炎症とWntシグナルとの関連も新たな研究領域になりつつある．さらに，Wntシグナル経路の活性を調節することによるがんの治療戦略も考案されてきている．(著者抄録)
(キーワード): Laminin *胃腫瘍幹細胞 *大腸腫瘍リン酸化カルシウムシグナル伝達 Beta Catenin G-Protein-Coupled Receptors *Wntシグナル伝達経路 Axin Protein 分子標的治療 Wnt-5a Protein Laminin Gamma 2 LGR5 Protein ヒトマウス動物

松本真司, 菊池章, 佐藤朗 :
【秒進分歩する癌研究と分子標的治療発癌から浸潤・転移に至るメカニズム解明とトランスレーショナルリサーチの最前線】基礎研究編:発癌から浸潤・転移に至るメカニズム解明発癌シグナルの原因究明 Wntシグナルネットワークの異常と癌,
実験医学, Vol.29, No.2, 170-179, 2011年2月.

(要約): ショウジョウバエの遺伝学に端を発したWnt研究は，腫瘍医学や発生生物学においても解析が進み，多様な研究領域に展開した．Wntは生物種を越えて保存されており，動物の発生に必須な分泌タンパク質である．Wntは細胞膜受容体に結合することにより，多彩な細胞内シグナル経路を活性化し，細胞の増殖や分化，運動，極性を制御する．したがって，Wntシグナル経路の異常が種々の疾患の原因となりうる．特に，Wntシグナル経路の構成タンパク質の遺伝子異常や発現異常がヒト癌の発症や悪性化に関与することが明らかになってきている．また，Wntシグナル経路の活性を調節することによる癌の治療戦略も考案されてきている．(著者抄録)
(キーワード): Laminin *シグナル伝達腫瘍遺伝子発現調節細胞運動 *腫瘍腫瘍侵入性変異リガンド腫瘍過程細胞極性 Beta Catenin 医薬品開発 *Wnt Proteins Wnt-5a Protein Laminin Gamma 2 ヒト動物

Akira Kikuchi, Hideki Yamamoto, Akira Sato and Shinji Matsumoto :
New insights into the mechanism of Wnt signaling pathway activation.,
International Review of Cell and Molecular Biology, Vol.291, 21-71, 2011.

(要約): Wnts compromise a large family of secreted, hydrophobic glycoproteins that control a variety of developmental and adult processes in all metazoan organisms. Recent advances in the Wnt-signal studies have revealed that distinct Wnts activate multiple intracellular cascades that regulate cellular proliferation, differentiation, migration, and polarity. Although the mechanism by which Wnts regulate different pathways selectively remains to be clarified, evidence has accumulated that in addition to the formation of ligand-receptor pairs, phosphorylation of receptors, receptor-mediated endocytosis, acidification, and the presence of cofactors, such as heparan sulfate proteoglycans, are also involved in the activation of specific Wnt pathways. Here, we review the mechanism of activation in Wnt signaling initiated on the cell-surface membrane. In addition, the mechanisms for fine-tuning by cross talk between Wnt and other signaling are also discussed.
(キーワード): Animals / Cyclic AMP-Dependent Protein Kinases / Endocytosis / Humans / Ligands / Models, Biological / NF-kappa B / Protein Isoforms / Protein Processing, Post-Translational / Receptors, Cell Surface / Receptors, Notch / TOR Serine-Threonine Kinases / Transforming Growth Factor beta / Wnt Proteins / Wnt Signaling Pathway / beta Catenin
(出版サイトへのリンク): ● Publication site (DOI): 10.1016/B978-0-12-386035-4.00002-1
(文献検索サイトへのリンク): ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 22017973; ● Search Scopus @ Elsevier (PMID): 22017973; ● Search Scopus @ Elsevier (DOI): 10.1016/B978-0-12-386035-4.00002-1

(DOI: 10.1016/B978-0-12-386035-4.00002-1, PubMed: 22017973) 松本真司, 岡本哲治, 菊池章 :
β-カテニン非依存性 Wnt シグナルによる細胞運動・極性および形態形成制御,
組織培養研究, Vol.28, No.2+3+4, 117-128, 2009年.

(出版サイトへのリンク): ● Publication site (DOI): 10.11418/jtca.28.117
(文献検索サイトへのリンク): ● CiNii @ 国立情報学研究所 (CRID): 1390001204922938624; ● Search Scopus @ Elsevier (DOI): 10.11418/jtca.28.117

(DOI: 10.11418/jtca.28.117, CiNii: 1390001204922938624)

講演・発表

Kikuchi Akira, Shinji Matsumoto and Harada Akikazu :
Oncogenic transcription difference between Wnt signal-activated hepatocellular carcinoma and colorectal carcinoma.,
Gordon Conference, Jul. 2023. Shinji Matsumoto, Harada Akikazu and Kikuchi Akira :
GREB1 drives HNF4α-dependent oncogenic transcription and tumor growth in Wnt signal-activated hepatocellular carcinoma.,
EMBO Workshop Wnt Meeting 2022., Nov. 2022. Kikuchi Akira and Shinji Matsumoto :
Regulation of cell adhesion and migration by Wnt5a signaling.,
Euro Wnt meeting 2009., Aug. 2009. Shinji Matsumoto :
Dishevelled/APC complex regulates cell adhesion and migration through mobilizing FAK and Paxillin.,
The Japan-Korea Joint Symposium on Wnt Signaling and Human Diseases., Nov. 2008. 松本真司, 原田武志, 菊池章 :
腺組織におけるWntシグナル誘導性の扁平円柱前駆細胞の同定と組織構築における役割.,
第96回日本生化学会大会シンポジウム, 2023年11月. 松本真司 :
上皮組織の形態形成制御とその異常による腫瘍化機構の解明,
第93回日本生化学会大会奨励賞受賞講演, 2021年9月. 松本真司 :
唾液腺におけるWntシグナル依存性新規前駆細胞の同定と機能解析,
第60回歯科基礎医学会学術大会アップデートシンポジウム, 2018年9月. 松本真司, 藤井慎介, 原田武志, 菊池章 :
低分子量Gタンパク質Arl4cによる上皮の形づくりと発がんの制御,
第89回日本生化学会大会シンポジウム, 2016年9月. 松本真司 :
WntとKITシグナルの活性化バランスによる唾液腺の形づくりと機能獲得過程の制御,
第58回歯科基礎医学会学術大会サテライトシンポジウム, 2016年8月.

研究会・報告書: 研究者総覧に該当データはありませんでした。

特許: 菊池章, 松本真司, 小比賀聡, 笠原勇矢, 福本巧 : ARL4Cを標的分子とするアンチセンスオリゴヌクレオチド，及び当該アンチセンスオリゴヌクレオチドを使用した核酸医薬, 特願2020541264 (2019年9月), 特開WO2020050307 (2020年3月), 特許第7396577号 (2023年12月). 菊池章, 松本真司, 藤井慎介 : 癌治療用医薬組成物, 特願2014-190619 (2014年9月), 特開2015-231978 (2015年12月), 特許第6436477号 (2018年11月).
作品: 研究者総覧に該当データはありませんでした。
補助金・競争的資金: 研究者総覧に該当データはありませんでした。

その他: 研究者総覧に該当データはありませんでした。

研究者総覧で最新データを確認する

2024年10月23日更新

専門分野・研究分野: 生理学 (Physiology)
口腔分子生理学 (Molecular Oral Physiology)
分子細胞生物学 (Molecular and Cellular Biology)
分子腫瘍学 (Molecular Oncology)
所属学会・所属協会: 日本癌学会
歯科基礎医学会
日本生理学会
日本分子生物学会
日本生化学会
委員歴・役員歴: 研究者総覧に該当データはありませんでした。
受賞: 2009年4月, 学会賞 (日本口腔科学会)
2009年5月, 奨励賞 (日本組織培養学会)
2015年2月, 奨励賞 (口腔医科学フロンティア研究会)
2020年9月, 奨励賞 (公益社団法人日本生化学会)
2023年, Jeremy Jass Prize for Research Excellence in Pathology in 2021 (The Journal of Pathology)
活動: 研究者総覧に該当データはありませんでした。

リサーチマップで最新データを確認するＪグローバルで最新データを確認する

2024年10月20日更新

2024年10月19日更新

Ｊグローバル

Jグローバル最終確認日: 2024/10/19 01:02
氏名（漢字）: 松本真司
氏名（フリガナ）: マツモトシンジ
氏名（英字）: Matsumoto Shinji
所属機関: 徳島大学教授
大阪大学招へい教員
大阪大学招へい教員

リサーチマップ

researchmap最終確認日: 2024/10/20 01:12
氏名（漢字）: 松本真司
氏名（フリガナ）: マツモトシンジ
氏名（英字）: Matsumoto Shinji
プロフィール: リサーチマップAPIで取得できませんでした。
登録日時: 2020/9/7 13:23
更新日時: 2024/10/15 13:43
アバター画像URI: リサーチマップAPIで取得できませんでした。
ハンドル: リサーチマップAPIで取得できませんでした。
eメール: リサーチマップAPIで取得できませんでした。
eメール（その他）: リサーチマップAPIで取得できませんでした。
携帯メール: リサーチマップAPIで取得できませんでした。
性別: リサーチマップAPIで取得できませんでした。
没年月日: リサーチマップAPIで取得できませんでした。
所属ID: 0344000000
所属: 徳島大学
部署: 大学院医歯薬学研究部口腔生理学分野
職名: 教授
学位: 博士（歯学）
学位授与機関: 広島大学
URL: リサーチマップAPIで取得できませんでした。
科研費研究者番号: リサーチマップAPIで取得できませんでした。
Google Analytics ID: リサーチマップAPIで取得できませんでした。
ORCID ID: リサーチマップAPIで取得できませんでした。
その他の所属ID: リサーチマップAPIで取得できませんでした。
その他の所属名: リサーチマップAPIで取得できませんでした。
その他の所属部署: リサーチマップAPIで取得できませんでした。
その他の所属職名: リサーチマップAPIで取得できませんでした。
最近のエントリー: リサーチマップAPIで取得できませんでした。
Read会員ID: リサーチマップAPIで取得できませんでした。
経歴
受賞
Misc
論文
講演・口頭発表等: リサーチマップAPIで取得できませんでした。
書籍等出版物
研究キーワード
研究分野
所属学協会
担当経験のある科目
その他: リサーチマップAPIで取得できませんでした。
Works: リサーチマップAPIで取得できませんでした。
特許
学歴
委員歴: リサーチマップAPIで取得できませんでした。
社会貢献活動: リサーチマップAPIで取得できませんでした。

ＫＡＫＥＮで最新データを確認する

2024年10月19日更新

研究者番号: 20572324

所属（現在）: 2024/4/1 : 徳島大学, 大学院医歯薬学研究部(歯学域), 教授

所属（過去の研究課題 情報に基づく）*注記: 2021/4/1 – 2023/4/1 : 大阪大学, 大学院医学系研究科, 准教授
2021/4/1 : 大阪大学, 医学系研究科, 准教授
2018/4/1 – 2020/4/1 : 大阪大学, 医学系研究科, 助教
2017/4/1 : 大阪大学, 医学(系)研究科(研究院), 助教
2016/4/1 : 大阪大学, 医学系研究科, 助教
2015/4/1 : 大阪大学, 医学(系)研究科(研究院), 特任助教 (常勤)
2015/4/1 : 大阪大学, 大学院医学系研究科, 特任助教
2013/4/1 – 2015/4/1 : 大阪大学, 医学(系)研究科(研究院), 特任助教(常勤)
2012/4/1 – 2014/4/1 : 大阪大学, 医学(系)研究科(研究院), 助教
2012/4/1 : 大阪大学, 医学系研究科, 助教
2011/4/1 : 大阪大学, 医学(系)研究科(研究院), 招へい研究員

審査区分/研究分野

研究代表者

生物系 / 医歯薬学 / 基礎医学 / 医化学一般
小区分49010:病態医化学関連
小区分50010:腫瘍生物学関連

研究代表者以外

生物系 / 総合生物 / 腫瘍学 / 腫瘍生物学
生物系
小区分50010:腫瘍生物学関連
中区分50:腫瘍学およびその関連分野
中区分48:生体の構造と機能およびその関連分野

キーワード

研究代表者

分枝管腔形成 / Wnt シグナル / Wntシグナル / 上皮 / Wnt / 極性 / EGF / Arｌ４ｃ / YAP/TAZ / 上皮管腔形成 / Arl4c / 上皮分岐管腔形成 / 外分泌腺 / 唾液腺 / 腺房 / 導管 / 分化 / KIT / 腺房分化 / 導管形成 / IQGAP1 / 膵がん / 転移 / KRas / MMP14 / アンチセンス核酸 / GREB1 / MT1-MMP / 細胞浸潤 / Ras / 小児固形がん / 神経芽腫

研究代表者以外

Wnt5a / Wntシグナル / がん / 炎症 / エンドサイトーシス / サイトカイン / 炎症性腸疾患 / エンドサイト―シス / シグナル伝達 / 癌 / 転移 / ハイスループットスクリーニング / 上皮菅腔組織形成 / 極性 / Arl4c / Dkk1 / Wnt / EGF / CKAP4 / 上皮管腔組織形成 / 細胞外基質 / 増殖因子 / HGF / FGF / 上皮管腔形成 / 肝細胞癌 / DKK1 / オルガノイド / 肝細胞癌サブタイプ / 線維芽細胞 / 大腸がん / 1細胞シーケンス / 大腸炎 / TGFβ / 腸管炎症 / 組織幹細胞 / 腺組織 / 扁平上皮組織 / AQP3 / 唾液腺 / 腺細胞 / 扁平上皮 / 食道 / ジフテリア毒素 / CXCR2 / 細胞生物学

研究課題研究成果共同研究者

「研究課題をさがす」で表示
テキスト（CSV）で出力

テキスト（CSV）で出力

注目研究はありません。

研究者を探す

松本 真司

Ｊグローバル

リサーチマップ

研究代表者

研究代表者以外

研究代表者

研究代表者以外

松本真司