2023 Fiscal Year Final Research Report
Molecular mechanism of epithelial-mesenchymal transition induced by EGFR tyrosine kinase inhibitors and development of EMT suppression therapy
| Project/Area Number |
21K07106
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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 | Tokyo Medical University |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
川原 玄理 東京医科大学, 医学部, 准教授 (40743331)
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| Project Period (FY) |
2021-04-01 – 2024-03-31
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| Keywords | がん / チロシンキナーゼ阻害薬 / 上皮間葉転換 / 浸潤・転移 / アクチン細胞骨格 |
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| Outline of Final Research Achievements |
Cyclin G-associated kinase (GAK), a secondary target molecule of the tyrosine kinase inhibitor (TKI) gefitinib, has been demonstrated to suppress epithelial-mesenchymal transition (EMT) in cancer cells. It has also been shown that the inhibition of EMT by GAK is related to the kinase activity of GAK, suggesting that TKIs such as gefitinib, which inhibit the kinase activity of GAK, may induce EMT and induce invasion and metastasis of cancer cells. In addition, it has become clear that GAK regulates myosin phosphatase as a molecular mechanism involved in the reorganization of the actin cytoskeleton, one of the characteristics of EMT, and a new pathway has been presented to develop EMT suppression therapy.
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| Free Research Field |
分子腫瘍学
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| Academic Significance and Societal Importance of the Research Achievements |
GAKの生理機能としては、エンドサイトーシスや細胞周期制御に関わることが報告されており、我々の解析でオートファジー制御にも関わることが示されていたが、EMTや、がんの浸潤・転移との関連は不明であった。本研究では、GAKがEMTに対して抑制的に働くことが明らかとなり、その分子機序の一端が明らかとなった。生理的・病理的に重要なプロセスであるEMTの分子基盤について、統合的理解の深化に繋がる成果と考えられる。また今後、浸潤・転移の予防・抑制によるがんの克服と、臓器の線維化などEMTを背景とする臨床課題への応用展開に結びつく可能性を提示する成果としても重要である。
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