Transcriptional regulation by TGF-beta signaling and its relation to progression of cancer

2020 Fiscal Year Final Research Report

• Project/Area Number: 15H05774
• Research Category: Grant-in-Aid for Scientific Research (S)
• Allocation Type: Single-year Grants
• Research Field: Tumor biology
• Research Institution: The University of Tokyo
• Principal Investigator: MIYAZONO Kohei 東京大学, 大学院医学系研究科(医学部), 教授 (90209908)
• Project Period (FY): 2015-05-29 – 2020-03-31
• Keywords: 細胞内シグナル伝達 / 細胞医化学 / がん微小環境 / がん幹細胞 / ゲノム科学

Outline of Final Research Achievements

In this project, we aimed to elucidate the various tumor-promoting effects of TGF-β. We found that active Ras greatly affects the expression profiles of TGF-β target genes, and that it acts as a switch in the conversion of TGF-β from tumor suppressor to tumor promoter. TGF-β induces epithelial-mesenchymal transition (EMT). In this project, we found that EMT affects the expression of inflammation-related genes. Furthermore, we showed that long-term TGF-β stimulation stabilizes the EMT phenotype. Using a tissue-clearing technology, we found that TGF-β is involved in intravasation in the primary tumor as well as in the extravasation of cancer cells in the blood vessels at distant organs. In metastatic foci, TGF-β-stimulated cells contribute to the formation of metastatic niches, and TGF-β may play a critical role in the formation of metastatic colonies.

Free Research Field

腫瘍生物学

Academic Significance and Societal Importance of the Research Achievements

本研究課題の成果による論文は広く引用され、組織透明化技術によるがんの転移機構の解析の成果は国内外のマスコミにも数多く取り上げられ注目された。本研究によりTGF-βが進行したがんにおいてがんの浸潤・転移の複数の段階でその進展を促進する分子機構が明らかとなった。これにより、TGF-βやRasなどのシグナルの制御を組み合わせることで進行がんの治療法の開発が可能になると期待された。