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Role of YAP1/TAZ in cell competition

Research Project

Project/Area Number 16K08626
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Pathological medical chemistry
Research InstitutionKobe University

Principal Investigator

Nishio Miki  神戸大学, 医学研究科, 講師 (10467897)

Research Collaborator MIYACHI Yosuke  
OTANI Junji  
TANE Shoji  
OMORI Hirofumi  
UEDA Fumihito  
MAEHAMA Tomohiko  
SUZUKI Akira  
Project Period (FY) 2016-04-01 – 2019-03-31
Project Status Completed (Fiscal Year 2018)
Budget Amount *help
¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000)
Fiscal Year 2018: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2017: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2016: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
KeywordsYAP1 / 細胞競合 / 細胞間コミュニケーション / Hippo経路 / 接着分子 / Hippo
Outline of Final Research Achievements

In mammalian cells, the cell with constitutively active YAP became "loser" and eliminated by the cell competition. This type of cell competition was observed in NIH3T3 cell and PAM cell in addition to previously reported MDCK cell. YAP-activated cells were prone to extrude and form a multi-stacked cell layer, when cultured with wild-type cells that were tightly attached to culture vessels and grew within flat monolayer. In contrast, when cultured on low-binding culture vessels, the YAP-activated cells turned to be "winner", because YAP-activated cells retained proliferation ability in anchorage-independent manner but wild-type cells did not. Intriguingly, in both cases, ECM coating of culture vessels strengthened binding of "loser" cells to the vessels and restored their proliferation, blunting "loser" cell elimination by cell competition. These observations suggest that the binding of cells to culture vessels and ECM may play a role in cell competition of mammalian cells.

Academic Significance and Societal Importance of the Research Achievements

異なる形質を有する同種の細胞間で適応度の高い細胞が生き残り、適応度の低い細胞が排除される「競合」現象が生じることが哺乳類細胞においても報告されたが、この細胞間コミュニケーション制御機構に関与する遺伝子群はほとんど分かっていなかった。本研究ではこの細胞間「競合」現象におけるYAP1の役割を詳細に解析することで、哺乳類細胞の細胞間コミュニケーション制御機構におけるHippo経路の関与を明らかにした。

Report

(4 results)
  • 2018 Annual Research Report   Final Research Report ( PDF )
  • 2017 Research-status Report
  • 2016 Research-status Report
  • Research Products

    (15 results)

All 2019 2018 2017 2016

All Journal Article (8 results) (of which Int'l Joint Research: 4 results,  Peer Reviewed: 8 results,  Open Access: 8 results,  Acknowledgement Compliant: 1 results) Presentation (7 results) (of which Invited: 4 results)

  • [Journal Article] Hippo pathway controls cell adhesion and context-dependent cell competition to influence skin engraftment efficiency2019

    • Author(s)
      Nishio Miki、Miyachi Yousuke、Otani Junji、Tane Shoji、Omori Hirofumi、Ueda Fumihito、Togashi Hideru、Sasaki Takehiko、Mak Tak Wah、Nakao Kazuwa、Fujita Yasuyuki、Nishina Hiroshi、Maehama Tomohiko、Suzuki Akira
    • Journal Title

      The FASEB Journal

      Volume: 33 Issue: 4 Pages: 5548-5560

    • DOI

      10.1096/fj.201802005r

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Loss of Mob1a/b in mice results in chondrodysplasia due to YAP1/TAZ-TEAD-dependent repression of SOX9.2018

    • Author(s)
      Goto H, Nishio M, To Y, Oishi T, Miyachi Y, Maehama T, Nishina H, Akiyama H, Mak TW, Makii Y, Saito T, Yasoda A, Tsumaki N, Suzuki A.
    • Journal Title

      Development

      Volume: 145 Issue: 6 Pages: 159244-159244

    • DOI

      10.1242/dev.159244

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Antitumor effects of the antiparasitic agent ivermectin via inhibition of Yes-associated protein 1 expression in gastric cancer.2017

    • Author(s)
      Nambara S, Masuda T, Nishio M, Kuramitsu S, Tobo T, Ogawa Y, Hu Q, Iguchi T, Kuroda Y, Ito S, Eguchi H, Sugimachi K, Saeki H, Oki E, Maehara Y, Suzuki A, Mimori K
    • Journal Title

      Oncotarget.

      Volume: 8(64) Issue: 64 Pages: 107666-107677

    • DOI

      10.18632/oncotarget.22587

    • NAID

      120006454566

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] YAP determines the cell fate of injured mouse hepatocytes in vivo2017

    • Author(s)
      Miyamura N, Hata S, Itoh T, Tanaka M, Nishio M, Itoh M, Ogawa Y, Terai S, Sakaida I, Suzuki A, Miyajima A, Nishina H.
    • Journal Title

      Nat Commun

      Volume: 8 Issue: 1 Pages: 16017-16017

    • DOI

      10.1038/ncomms16017

    • NAID

      120006373756

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Hippo vs. Crab: tissue-specific functions of the mammalian Hippo pathway2017

    • Author(s)
      M. Nishio, T. Maehama, H. Goto, K. Nakatani, W. Kato, H. Omori, Y. Miyachi, H. Togashi, Y. Shimono and A. Suzuki
    • Journal Title

      Genes to Cells

      Volume: 22 Issue: 1 Pages: 6-31

    • DOI

      10.1111/gtc.12461

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Altered expression of Hippo signaling pathway molecules in intrahepatic cholangiocarcinoma.2017

    • Author(s)
      Sugimachi K, Nishio M, Aishima S, Kuroda Y, Iguchi T, Komatsu H, Hirata H, Sakimura S, Eguchi H, Bekki Y, Takenaka K, Maehara Y, Suzuki A, Mimori K.
    • Journal Title

      ONCOLOGY

      Volume: - Issue: 1 Pages: 67-74

    • DOI

      10.1159/000463390

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] MOB1-YAP1/TAZ-NKX2.1 axis controls bronchioalveolar cell differentiation, adhesion and tumour formation. Oncogene2017

    • Author(s)
      Otsubo K, Goto H, Nishio M, Kawamura K, Yanagi S, Nishie W, Sasaki T, Maehama T, Nishina H, Mimori K, Nakano T, Shimizu H, Mak TW, Nakao K, Nakanishi Y, Suzuki A
    • Journal Title

      Oncogene

      Volume: 印刷中 Issue: 29 Pages: 4201-4211

    • DOI

      10.1038/onc.2017.58

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
  • [Journal Article] Hyperactive mTOR signals in the proopiomelanocortin-expressing hippocampal neurons cause age-dependent epilepsy and premature death in mice.2016

    • Author(s)
      Matsushita Y, Sakai Y, Shimmura M, Shigeto H, Nishio M, Akamine S, Sanefuji M, Ishizaki Y, Torisu H, Nakabeppu Y, Suzuki A, Takada H, Hara T.
    • Journal Title

      Sci Rep

      Volume: 未 Issue: 1 Pages: 22991-22991

    • DOI

      10.1038/srep22991

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Presentation] Hippo経路とその破綻病態2018

    • Author(s)
      西尾美希、大森裕文、藤 庸子、中谷圭佑、青野ゆかり、清野 透、益田宗幸、中川尚志、片渕秀隆、田代浩徳、前濱朝彦、鈴木 聡
    • Organizer
      第41回日本分子生物学会年会(MBSJ2018)
    • Related Report
      2018 Annual Research Report
    • Invited
  • [Presentation] Hippo経路分子Mob1変異による肝がん発症機構2017

    • Author(s)
      西尾美希、杉町圭史、新家一男、三森功士、鈴木 聡
    • Organizer
      第54回 日本臨床分子医学会学術集会
    • Related Report
      2017 Research-status Report
  • [Presentation] Hippo signaling pathway affects cell competion in mammalian cells via cell-ECM binding and anchorage-dependent cell proliferation2017

    • Author(s)
      Miki Nishio, Tomohiko Maehama, Akira Suzuki
    • Organizer
      3rd International Symposium on Cell Competition
    • Related Report
      2017 Research-status Report
  • [Presentation] Hippoシグナル経路による細胞増殖変化と細胞間コミュニケーション2017

    • Author(s)
      西尾美希、前濱朝彦、上田史仁、鈴木聡
    • Organizer
      新学術領域「幹細胞老化と疾患」「細胞競合」総括班主催「若手の会」
    • Related Report
      2017 Research-status Report
  • [Presentation] Role of Hippo pathway in vivo2016

    • Author(s)
      Miki Nishio, Hiroki Goto, Kohei Otsubo, Hideru Togashi, Yohei Shimono, Tomohiko Maehama, Akira Suzuki
    • Organizer
      第75回日本癌学会学術総会
    • Place of Presentation
      横浜
    • Year and Date
      2016-10-06
    • Related Report
      2016 Research-status Report
    • Invited
  • [Presentation] The Hippo signaling Pathway: Function, Disorders, and Therapeutic Targeting2016

    • Author(s)
      Miki Nishio, Hiroki Goto, Yousuke Miyachi, Hideru Togashi, Yohei Shimono, Akira Suzuki
    • Organizer
      The 89th Annual Meeting of the Japanese Biochemical Society
    • Place of Presentation
      仙台
    • Year and Date
      2016-09-25
    • Related Report
      2016 Research-status Report
    • Invited
  • [Presentation] 遺伝子改変動物を利用した,形態形成におけるHippo経路の機能解析2016

    • Author(s)
      田中雅人, 後藤裕樹, 西尾美希, 中谷圭佑, 前濱朝彦, 富樫 英, 下野洋平, 鈴木 聡
    • Organizer
      第48回日本臨床分子形態学会
    • Place of Presentation
      熊本
    • Year and Date
      2016-09-23
    • Related Report
      2016 Research-status Report
    • Invited

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Published: 2016-04-21   Modified: 2020-03-30  

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