2018 Fiscal Year Final Research Report
Role of Hippo signaling in cell competition
| Project Area | Cell competition: a mechanism for survival of the fittest in the multi-cellular community |
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| Project/Area Number |
26114005
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| Research Category |
Grant-in-Aid for Scientific Research on Innovative Areas (Research in a proposed research area)
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| Allocation Type | Single-year Grants |
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| Review Section |
Biological Sciences
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| Research Institution | Kobe University (2016-2018)
Kyushu University (2014-2015) |
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Principal Investigator |
Suzuki Akira 神戸大学, 医学研究科, 教授 (10311565)
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| Co-Investigator(Kenkyū-buntansha) |
仁科 博史 東京医科歯科大学, 難治疾患研究所, 教授 (60212122)
後藤 裕樹 九州大学, 生体防御医学研究所, 助教 (20734495)
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| Research Collaborator |
Maehama Tomohiko
Nishio Miki
Miyamura Norio
Ishihara Erika
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| Project Period (FY) |
2014-07-10 – 2019-03-31
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| Keywords | Hippo / YAP1 / 細胞競合 / cell competition |
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| Outline of Final Research Achievements |
Cells overexpressing active YAP undergo apical extrusion and are losers in competitions with normal cells. However, YAP overexpressing cells switched from losers to winners when cocultured with cells expressing Ras or Src. YAP overexpressing cells show decrease in cell-matrix adhesion, and cell adhesion mediated proliferation. However, they proliferate faster than control cells when co-cultured in dishes impeding cell adhesion. Thus, the role of YAP in cell competitions is context dependent in vitro.
In vivo, YAP activation in damaged hepatocytes promotes their elimination by in vivo liver mosaic analysis, and YAP activated epidermis cannot be engrafted onto donor mice and shrink away from control skin. In contrast, YAP activation in undamaged hepatocytes leads to proliferation. Thus, the role of YAP is context dependent also in vivo. Our results thus uncover the mechanism by which YAP influences cell competition, that is important for liver or skin grafting, or cancer progression.
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| Free Research Field |
細胞生物学、腫瘍学
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| Academic Significance and Societal Importance of the Research Achievements |
細胞競合におけるHippo経路の役割を詳細に解明した。本研究によって細胞競合の本質の一端を明らかにしたことのみならず、Hippo経路の制御によって、細胞競合現象を介した、肝臓や皮膚移植効率の向上に介入できることを始めて提唱した。
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