Molecular mechanisms of CLDN-ER axis regulating the breast and endometrial cancer progression

2020 Fiscal Year Final Research Report

• Project/Area Number: 19K16615
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 49030:Experimental pathology-related
• Research Institution: Fukushima Medical University
• Principal Investigator: Sugimoto Kotaro 福島県立医科大学, 医学部, 講師 (40791009)
• Project Period (FY): 2019-04-01 – 2021-03-31
• Keywords: がん / 細胞間接着 / 核内受容体 / 乳癌 / 子宮体癌

Outline of Final Research Achievements

We discovered a novel signaling pathway from the tight junction protein claudin-6 and ending to nuclear receptors, which triggers the epithelial differentiation of stem cells. We subsequently showed that claudin-6 is a poor prognostic factor for uterine cancer. In addition, we found that the mechanism is due to the abnormal activation of a signaling pathway between claudin-6 and estrogen receptor-alpha, one of the nuclear receptors. On the other hand, in breast cancer, abnormal activation and its involvement in cancer progression of the signal from claudin-4 to another nuclear receptor, the liver X receptor, has also been suggested.

Free Research Field

実験病理学

Academic Significance and Societal Importance of the Research Achievements

核内受容体は天然の脂質リガンドによって活性化されるが、リン酸化などの翻訳後修飾によっても制御されている。前者は比較的よく研究されていたが、後者はあまりよく解っていない。本研究では核内受容体の異常リン酸化が腫瘍の悪性形質制御に影響することを明らかにし、これが新規診断マーカーであると共に潜在的な治療標的である可能性が示唆された。本研究は新規創薬など個別化がん治療戦略の発展に寄与するものである。