| Project/Area Number |
17K15597
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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 |
General medical chemistry
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| Research Institution | Kobe University |
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Principal Investigator |
Kedashiro Shin 神戸大学, 医学研究科, 特命助教 (00754558)
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| Project Period (FY) |
2017-04-01 – 2020-03-31
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| Project Status |
Completed (Fiscal Year 2019)
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| Budget Amount *help |
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2018: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
Fiscal Year 2017: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
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| Keywords | Necl-4 / ErbB3 / Necl-2 |
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| Outline of Final Research Achievements |
The ligand-induced dimerization of cell surface single-transmembrane receptors is essential for their activation. ErbB3, a single-transmembrane receptor, binds to its ligand heregulin, leading to the hetero-dimerization with ErbB2. This dimerization induces the activation of the signaling pathways for cell movement and survival. Despite the essential roles of ErbB3 signaling for cell survival, its hyperactivation and overexpression cause tumorigenesis. In this study, it was elucidated that Necl-4, nectin-like molecule-4/cell adhesion molecule 4, known to serve as a tumor suppressor, interacts with ErbB3 and inhibits the ErbB3/ErbB2 hetero-dimerization in an allosteric manner. Necl-4 also interacted with the hepatocyte growth factor receptor c-Met and reduced its phosphorylation, suggesting that Necl-4 targets the various oncogenic cell surface receptors to suppress the tumorigenesis.
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| Academic Significance and Societal Importance of the Research Achievements |
現在、日本では二人に一人はがんになると言われており、その発症や、がん細胞の転移や生存の仕組みの解明は喫緊の課題である。事実、様々な抗がん剤がその仕組みを標的とし、積極的に開発されている。細胞膜受容体ErbB3は、乳がんを含む多くのがんにおいて、その転移や生存を促進するタンパク質として知られている。ErbB3の働きを抑える機能を持つ分子として、細胞接着分子Necl-4を明らかにし、Necl-4によるErbB3の制御機構を解明した。この成果は、ErbB3に対する新規抗がん剤の開発に役立つと期待される。
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