2022 Fiscal Year Final Research Report
Identification of phosphoproteins contributing to Epithelial-Mesenchymal Transition.
| Project/Area Number |
17K08648
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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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| Research Field |
General medical chemistry
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| Research Institution | Kitasato University |
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Principal Investigator |
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| Project Period (FY) |
2017-04-01 – 2023-03-31
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| Keywords | EMT / チロシンリン酸化 |
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| Outline of Final Research Achievements |
Long-term TGF-β stimulation of epithelial cells induces myofibroblast-like changes (EMyoT), and co-stimulation of TGF-β and FGF-2 enhances EMT (eEMT). Therefore, this study aimed to reveal the phosphorylation signaling pathway involved in the induction of eEMT. Comprehensive shotgun proteomic analysis revealed approximately 250 elevated protein expression in EMyoT and eEMT, respectively, and a combined search using the SILAC method and purification with tyrosine phosphorylation antibodies revealed approximately 800 distinct protein phosphorylations in EMyoT and eEMT. Knockdown of multiple eEMT-specific phosphoproteins did not reveal any change in eEMT inducibility, but inhibitors of Axl suppressed eEMT induction.
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| Free Research Field |
分子細胞生物学
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| Academic Significance and Societal Importance of the Research Achievements |
TGF-βとFGF-2の長期曝露によるeEMTは創傷治癒部位や繊維化形成部位、がん微小環境など実際の生体内で誘導されている現象であることが推測できる。それ故、本研究で明らかにしたAxl阻害剤によるeEMT誘導の抑制は、EMTを標的とした治療法開発に繋がる可能性がある。また、SILAC法から新規に同定した123のeEMT特異的なチロシンリン酸化タンパク質の中にも線維化やがんの浸潤・転移促進に重要な未知のシグナル因子が含まれていることが予測される。
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