Development of treatment strategy targeting mechanisms mediated by TRIM family proteins

2022 Fiscal Year Final Research Report

• Project/Area Number: 20K08945
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 55010:General surgery and pediatric surgery-related
• Research Institution: The University of Tokyo (2021-2022); Tokyo Metropolitan Geriatric Hospital and Institute of Gerontology (2020)
• Principal Investigator: Azuma Kotaro 東京大学, 医学部附属病院, 講師 (30401110)
• Co-Investigator(Kenkyū-buntansha): 井上 聡 地方独立行政法人東京都健康長寿医療センター(東京都健康長寿医療センター研究所), 東京都健康長寿医療センター研究所, 研究部長 (40251251)
• Project Period (FY): 2020-04-01 – 2023-03-31
• Keywords: 乳がん / TRIM47 / TRIM25 / TRIM44 / TRIM39 / ユビキチン化 / スフェロイド培養

Outline of Final Research Achievements

The purpose of this research is to discover new mechanisms of Tripatite Motif (TRIM) family proteins related to breast cancer promotion and resistance to therapies. We also aim to develop new therapeutic strategy for breast cancer. Through the entire research period, we are successful in elucidating clinical significance and new function of TRIM family proteins including TRIM25, TRIM39, TRIM44, and TRIM47. We published papers on all the four molecules during the research period. One of the mechanisms was the stabilization of interacting protein by ubiquitination. We are also establishing primary cancer cell lines from breast cancer patients which can be used for further preclinical studies to test the strategies targeting TRIM family-related mechanisms.

Free Research Field

分子生物学

Academic Significance and Societal Importance of the Research Achievements

本研究においては、複数の乳癌の予後不良因子を蛋白質レベルで同定した。また、TRIM47の機能解析において、PKD3、PKC epsilonの安定化を介したメカニズムを示した点においても学術的な新規性を有する。さらに、ユビキチン分子のリジン27を介するポリユビキチン化という非典型的な分子修飾を示すことができた。本研究で同定した予後不良因子や関連蛋白質の知見を活用することにより、有効なオーダーメード医療を行う道が開け、現在の日本の乳癌の罹患率の高さや死亡数の増加傾向を鑑みると、社会的な意義も有しているといえる。