2023 Fiscal Year Final Research Report
Identification of tumor-promoting roles of the Hippo tumor-suppressing signaling
| Project/Area Number |
21K06543
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Review Section |
Basic Section 47030:Pharmaceutical hygiene and biochemistry-related
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| Research Institution | Chiba University |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
高野 博之 千葉大学, 大学院薬学研究院, 教授 (60334190)
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| Project Period (FY) |
2021-04-01 – 2024-03-31
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| Keywords | シグナル伝達 |
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| Outline of Final Research Achievements |
Hippo pathway is known as a tumor-suppressing signaling that negatively regulates YAP/TAZ, transcriptional cofactors for TEAD, via the protein kinases LATS1/2. In this study, we found that LATS1/2 have a role to activate VGLL3, another transcriptional cofactor for TEAD, and promote cell growth. Mechanistically, induction of the inflammatory cytokine IL-1α is involved in VGLL3-mediated cell growth. Furthermore, we found that VGLL3 has a role to enhance cell motility via induction of the transcriptional factor HMGA2. These results suggest that LATS1/2 act as tumor-promoting proteins in tumor cells in which VGLL3 is highly expressed.
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| Free Research Field |
生物系薬学
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| Academic Significance and Societal Importance of the Research Achievements |
本研究では、Hippo経路の中心的キナーゼLATS1/2の活性化が転写共役因子VGLL3の活性化を誘導し、細胞増殖性や運動性を亢進することを明らかにした。この成果の学術的意義は、がん抑制シグナル経路として広く知られるHippo経路が、がん細胞の状態の違いによりがん抑制とは逆のがん促進機能もつことを初めて明らかにしたことである。さらに、本成果によってLATS1/2の活性阻害ががん治療に応用できる可能性が示されたことは、がん克服を目指す社会において意義のある知見といえる。
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