2020 Fiscal Year Final Research Report

Roles of transcription factors role of transcription factors in the maintenance of endothelial identity

Research Project

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Project/Area Number	17K07157
Research Category	Grant-in-Aid for Scientific Research (C)
Allocation Type	Multi-year Fund
Section	一般
Research Field	Tumor biology
Research Institution	Niigata University (2019-2020) Tokyo Medical and Dental University (2017-2018)
Principal Investigator	Yoshimatsu Yasuhiro 新潟大学, 医歯学系, 准教授 (60586684)
Project Period (FY)	2017-04-01 – 2021-03-31
Keywords	がん関連線維芽細胞 / 血管 / 血管内皮細胞 / 間葉系細胞 / 内皮間葉移行 / TGF-β / Activin / Etsファミリー転写因子
Outline of Final Research Achievements	A subset of fibroblasts, which are involved in the malignant progression of various diseases, differentiate from endothelial cells through a phenomenon called endothelial-mesenchymal transition. However, the role and molecular mechanism of the endothelial differentiation remain unclear. Therefore, we attempted to elucidate it in this study. Hypothesizing that transcription factors are necessary for endothelial cells to maintain their properties as endothelial cells without undergoing endothelial-mesenchymal transition, we identified an Ets family transcription factor that functions in blood vascular endothelial cells. We also found that a different Ets family transcription factor is important in lymphatic endothelial cells, which are a different type of endothelial cells. In addition, we were able to identify different endogenous cytokines as accelerators of endothelial-mesenchymal transition that are regulated by these transcription factors, respectively.
Free Research Field	腫瘍生物学・血管生物学
Academic Significance and Societal Importance of the Research Achievements	今回解明されたEndMT抑制因子としてのEtsファミリー転写因子の役割から、内皮細胞から線維芽細胞へと分化する際には、Etsファミリーを含む複数の転写因子によってそれぞれの細胞マーカーの発現が制御を受けることが明らかになり、複雑な転写ネットワークが存在することが示唆された。腫瘍血管内皮細胞やがん関連線維芽細胞は特に正常のそれとは非常に異なる性質を持つことが知られており、腫瘍における特異な生命現象の理解に大きく貢献したと考えられる。さらに今回このEndMTに関与することが示された分子群は、がんにおける新たな標的分子や診断マーカーになる可能性があり、がんの分子標的治療の選択肢を広げた意義は大きい。