| Project/Area Number |
16K18412
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| Research Category |
Grant-in-Aid for Young Scientists (B)
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| Allocation Type | Multi-year Fund |
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| Research Field |
Tumor biology
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| Research Institution | The University of Tokyo |
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Principal Investigator |
Ito Takeshi 東京大学, 医科学研究所, 助教 (20733075)
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| Project Period (FY) |
2016-04-01 – 2019-03-31
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| Project Status |
Completed (Fiscal Year 2018)
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| Budget Amount *help |
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2018: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2017: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2016: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
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| Keywords | Hippo経路 / 細胞接着 / 肺腺がん / 腫瘍生物学 |
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| Outline of Final Research Achievements |
Hippo pathway is involved in the regulation of contact inhibition and organ size control by sensing cell density through adhesion receptors in Drosophila, but the receptors have not been identified in mammalian cells. In this study, we showed that CADM1, an immunoglobulin superfamily cell adhesion molecule, enhanced YAP1 phosphorylation and repressed the expression of YAP1 target genes through interaction with multiple Hippo pathway components. These results suggest that CADM1 would function as an adhesion receptor of Hippo pathway in mammalian cells.
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| Academic Significance and Societal Importance of the Research Achievements |
哺乳細胞におけるHippo経路の受容体は同定されておらず、細胞接着を感知しMST-LATSキナーゼカスケードの活性化に至るまでの分子機構は空白地帯となっていた。本研究はCADM1がHippo経路の接着受容体として機能し、足場タンパク質NF2, KIBRA, SAV1、キナーゼMST1/2, LATS1/2との相互作用を介してHippo経路を活性化するという分子機構を初めて示した点に大きな学術的意義がある。
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