Mechanism of tight junction attenuation by STIL and its application to the pathological diagnosis of ductal carcinoma in situ of the breast

2023 Fiscal Year Final Research Report

• Project/Area Number: 20K16205
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 49020:Human pathology-related
• Research Institution: Aichi Medical University
• Principal Investigator: Hideaki Ito 愛知医科大学, 医学部, 講師 (90711276)
• Project Period (FY): 2020-04-01 – 2024-03-31
• Keywords: 乳癌 / タイトジャンクション / STIL / 浸潤

Outline of Final Research Achievements

The aim of this study was to elucidate the molecular mechanisms in the transition from non-invasive to invasive breast ductal carcinoma, based on the mechanism of tight junction attenuation by STIL, and to apply this to the selection of cases with high potential for invasive cancer transition.After STIL knockdown, tight junctions in breast cancer cells were enhanced. Furthermore, STIL was found to interact with TRAF4, which has been reported to have a tight junction attenuating effect; STIL may alter the localisation of tight junction-associated factors, including TRAF4, and act to attenuate tight junctions. Assessing them in the histopathology of ductal carcinoma in situ could be applied to invasive risk assessment.

Free Research Field

人体病理学

Academic Significance and Societal Importance of the Research Achievements

本研究では、細胞結合の一つであるタイトジャンクションの減弱メカニズムから、乳癌浸潤メカニズムの迫り、またこれまでにない非浸潤性乳管癌の浸潤リスク評価法の確立を目指した。その成果として、中心小体複製関連因子STILが乳癌の進展に関わっている可能性を見出した。本成果は乳癌の浸潤メカニズム解明の一助となり、また本成果を基盤的知見とし、STIL及びTRAF4の発現や相互作用を病理組織で評価することで、乳癌病理診断に応用できる可能性があると考えている。