Mechanisms of Met specific signaling for cancer malignancy mediated by a novel target molecule PLEKHA5
| Project/Area Number |
18K07219
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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 50010:Tumor biology-related
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| Research Institution | Sasaki Foundation |
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Principal Investigator |
Yamaguchi Hideki 公益財団法人佐々木研究所, 附属研究所, 部長(移行) (10345035)
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| Co-Investigator(Kenkyū-buntansha) |
今井 俊夫 国立研究開発法人国立がん研究センター, 研究所, 施設長 (20342884)
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| Project Period (FY) |
2018-04-01 – 2021-03-31
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| Project Status |
Completed (Fiscal Year 2020)
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| Budget Amount *help |
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2020: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2019: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2018: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
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| Keywords | Met / PLEKHA5 / スキルス胃癌 / 腹膜播種 / 腹膜播種性転移 / リン酸化 / シグナル伝達 |
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| Outline of Final Research Achievements |
Met is a receptor tyrosine kinase and its aberrant activation has been found in a variety of carcinomas. Met has been implicated in tumor malignancy, including metastasis, recurrence, and drug resistance. We previously identified a protein called PLEKHA5 with unknown function by phosphoproteomic analysis of scirrhous gastric carcinoma (SGC) cells possessing Met gene amplification. We also revealed that knockdown of PLEKHA5 suppresses the growth, invasion, and metastasis of SGC cells. In this study, we found that PLEKHA5 is tyrosine-phosphorylated downstream of Met and regulates the survival of SGC cells with Met gene amplification. These results indicate that PLEKHA5 is a novel downstream effector of Met and may be a novel therapeutic target of SGC.
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| Academic Significance and Societal Importance of the Research Achievements |
Metは様々ながんで異常がみられるがん原遺伝子であり、現在多くのMet阻害剤が開発されている。しかし薬剤耐性が問題になっており、Metの下流で働く新たな治療標的の同定は重要な課題である。また、スキルス胃がんは日本に多い難治がんであり、特に腹腔内に種を播くように転移する腹膜播種を起こすことが、治療を困難にしている。本研究では、Metの新規下流分子としてPLEKHA5という分子を同定し、PLEKHA5がMet異常を持つスキルス胃がんの悪性化に必要であることを見出した。従って、本研究の成果は、スキルス胃がん含むMet異常を持つ様々ながんの新たな治療法の開発につながるものと期待される。
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Report
(4 results)
Research Products
(24 results)
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[Journal Article] MT1-MMP recruits the ER-Golgi SNARE Bet1 for efficient MT1-MMP transport to the plasma membrane.2019
Author(s)
Miyagawa, T.,* Hasegawa, K.,* Aoki, Y.,* Watanabe, T.,* Otagiri, Y., Arasaki, K., Wakana, Y., Asano, K., Tanaka, M., Yamaguchi, H., Tagaya, M. and Inoue, H. (*, These authors contributed equally to this work.)
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Journal Title
J. Cell Biol.
Volume: 218
Issue: 10
Pages: 3355-3371
DOI
Related Report
Peer Reviewed / Open Access
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