2020 Fiscal Year Final Research Report
S100A4/non-muscle Myosin II Signaling Regulates Epithelial-Mesenchymal Transition and Stemness in Uterine Carcinosarcoma
| Project/Area Number |
17K08703
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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 |
Human pathology
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| Research Institution | Kitasato University |
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Principal Investigator |
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| Project Period (FY) |
2017-04-01 – 2021-03-31
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| Keywords | 子宮癌肉腫 / S100A4 / ミオシン9 / 癌幹細胞 / 上皮間葉転換 |
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| Outline of Final Research Achievements |
In this study, we investigated the role of S100A4 and related molecules in uterine cancer sarcoma (UCS). Cells overexpressing S100A4 had the characteristics of cancer stem cells (CSC), showing decreased cell proliferation and increased migration. This change disappeared by knockdown of S100A4. In shotgun proteomics analysis, S100A4 was closely associated with non-myocyte myosin II (NMII). Specific inhibition of NMII by brevistatin induced overexpression of S100A4 and induced fibroblast-like changes. From the above, in UCS, the S100A4 / NMII signaling pathway induces EMT / CSC and is involved in the derivation of sarcoma components from cancer components and changes in growth and migration ability.
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| Free Research Field |
分子病理学
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| Academic Significance and Societal Importance of the Research Achievements |
極めて予後不良の子宮癌肉腫の発生の分子機構の１つにS100A4/NMIIA経路が関与することを立証したことに学術的意義がある。次のスッテプとして、この経路に対して抑制的に作用する小化学分子化合物を網羅的に検索して、子宮癌肉腫の新規治療法の開発に繋げることに社会的意義がある。
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