| Project/Area Number |
16K20974
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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 |
Tumor biology
General medical chemistry
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| Research Institution | The University of Tokyo |
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Principal Investigator |
AKAGI Yoko 東京大学, 大学院医学系研究科(医学部), 助教 (70771004)
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| Project Period (FY) |
2016-04-01 – 2018-03-31
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| Project Status |
Completed (Fiscal Year 2017)
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| Budget Amount *help |
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2017: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Fiscal Year 2016: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
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| Keywords | TGF-beta / 上皮間葉移行 / がん幹細胞 / PRMT1 / 抑制型Smad / EMT / Smad / cancer stem cell / シグナル伝達 / 癌 |
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| Outline of Final Research Achievements |
Tumors are composed of different cell types including cancer stem cells (CSCs), their heterogeneous progeny and the stromal cells. In contrast to classical model of CSC differentiation, epithelial cancer cells are now considered to have differentiation plasticity. Understanding the signaling networks that control the differentiation plasticity is essential to target cancer cells.
The epithelial-to-mesenchymal transdifferentiation (EMT) is an essential process in development, and is reactivated in cancer cells to promote invasion, contribute to cancer stroma formation, generate CSCs and decrease sensitivity to anticancer drugs. TGF-beta signaling, which is often activated in carcinomas, drives EMT of carcinoma cells.
This study provides evidence that an Arginine methyltransferase PRMT1 promotes the TGF-beta-induced EMT and epithelial stem cell generation through the methylation of Smad7. This mechanism may provide a new treatment strategy to target CSCs.
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