Project/Area Number |
16K08626
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Research Category |
Grant-in-Aid for Scientific Research (C)
|
Allocation Type | Multi-year Fund |
Section | 一般 |
Research Field |
Pathological medical chemistry
|
Research Institution | Kobe 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)
|
Keywords | YAP1 / 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。
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