Functional analysis of cancer-associated EMT in circulating tumor cells and oral cancer cells

2021 Fiscal Year Final Research Report

• Project/Area Number: 18H02969
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Review Section: Basic Section 57020:Oral pathobiological science-related
• Research Institution: University of Yamanashi
• Principal Investigator: Saitoh Masao 山梨大学, 大学院総合研究部, 教授 (90345041)
• Project Period (FY): 2018-04-01 – 2022-03-31
• Keywords: EMT / TGF-β / がん

Outline of Final Research Achievements

Snail and ZEB1/2 (ZEB1 and ZEB2), known as EMT transcription factors, are key regulators of this transition. ZEB1/2 are positively correlated with EMT phenotypes and the aggressiveness of cancers. On the other hand, Snail is also correlated with the aggressiveness of cancers, but is not correlated with the expression of EMT marker proteins. Snail is induced by transforming growth factor-β (TGF-β), a well-known inducer of EMT, in various cancer cells. Interestingly, Snail induction by TGF-β is markedly enhanced by active Ras signals. Thus, cancer cells harboring an active Ras mutation exhibit a drastic induction of Snail by TGF-β alone. Here, we found that members of the E26 transformation-specific (Ets) transcription factor family, Ets1 and Ets2, contribute to the upregulation of both Snail and ZEB1/2. Thus, Ets1 is a crucial molecule for regulating Snail and ZEB1/2, and thus cancer progression is mediated through post-translational modification of the exon VII domain.

Free Research Field

がん細胞生物

Academic Significance and Societal Importance of the Research Achievements

がん細胞は周囲の間質内に浸潤し、脈管内に侵入し、転移巣を形成する。この過程にEMTという現象が深く関与していることがわかっており、EMT転写因子によって制御されている。そこで本研究ではEMT転写因子の発現制御機構を検討し、Etsファミリー分子群が正と負に調節していることを見いだした。Ets1とEts2はEMTを促進する作用を、ESE1とESE3は抑制する作用を持っていた。したがって、原発巣でこれらの分子群の発現を検討することで、遠隔転移や循環内腫瘍細胞になりうる細胞を診断でき、悪性度をより詳細に評価できる点が学術的にまた社会的にも意義が高いところである。