Estrogen-related receptor alpha induces epithelial-mesenchymal transition through cancer-stromal interactions in endometrial cancer

2020 Fiscal Year Final Research Report

• Project/Area Number: 19K24049
• Research Category: Grant-in-Aid for Research Activity Start-up
• Allocation Type: Multi-year Fund
• Review Section: 0906:Surgery related to the biological and sensory functions and related fields
• Research Institution: Kyoto Prefectural University of Medicine
• Principal Investigator: Yoriki Kaori 京都府立医科大学, 医学(系)研究科(研究院), 助教 (70851682)
• Project Period (FY): 2019-08-30 – 2021-03-31
• Keywords: エストロゲン関連受容体 / 癌ー間質相互作用 / 上皮間葉転換 / 子宮体癌

Outline of Final Research Achievements

We investigated whether ERRα could participate in epithelial-mesenchymal transition (EMT) in endometrial cancer through cancer-stromal interactions. Two endometrial cancer cell lines were co-cultured with endometrial stromal cells (T-HESCs). EMT-associated factors including vimentin, Snail, and ZEB1 were upregulated in cancer cells overexpressing ERRα and that TGF-β was induced in T-HESCs. In contrast, ERRα knockdown suppressed EMT-associated factors in cancer cells and TGF-β in T-HESCs. ERRα overexpression increased EMT-associated factors after TGF-β exposure; however, it decreased E-cadherin at protein level. ERRα knockdown suppressed EMT-associated factors after TGF-β exposure, whereas E-cadherin remained unchanged. ERRα knockdown attenuated the stimulation of migration and invasion by TGF-β. ERRα is a potential target for inhibiting TGF-β-induced EMT through cancer-stromal interactions in endometrial cancer.

Free Research Field

婦人科腫瘍

Academic Significance and Societal Importance of the Research Achievements

子宮体癌の増殖や発癌にエストロゲンが深く関与するが、本疾患の病態はこれだけでは説明できず、新たな治療戦略確立にはその発癌・進展機構に基づいた分子機構の解明が必要である。エストロゲン関連受容体（ERRα）は子宮体癌の悪性化や進展維持作用をもつことが知られる。さらにERRαは癌微小環境において癌細胞のエネルギー代謝に関わる遺伝子発現を変化させることにより、低酸素などのストレス環境に適応しており、子宮体癌微小環境の構築に重要な役割を果たしている。本研究でERRαを介した癌細胞の転移・浸潤作用の分子メカニズムを解明できたことは、新たな癌微小環境選択的な子宮体癌治療法の開発への重要な糸口となる。