Study on novel mechanism of breast cancer development by modulation of mitochondrial control

2019 Fiscal Year Final Research Report

• Project/Area Number: 18K19473
• Research Category: Grant-in-Aid for Challenging Research (Exploratory)
• Allocation Type: Multi-year Fund
• Review Section: Medium-sized Section 50:Oncology and related fields
• Research Institution: Tokyo Medical and Dental University
• Principal Investigator: Miki Yoshio 東京医科歯科大学, 難治疾患研究所, 教授 (10281594)
• Co-Investigator(Kenkyū-buntansha): 砂田 成章 東京医科歯科大学, 難治疾患研究所, 助教 (70807677)
• Project Period (FY): 2018-06-29 – 2020-03-31
• Keywords: ミトコンドリア / マイトファジー / BRCA1, BRCA2 / Mfn

Outline of Final Research Achievements

A group of molecules including BRCA1 and BRCA2 was reported to function in the mitophagy pathway. Therefore, we analyzed a novel mechanism of breast cancer development by modulation of mitochondrial control. First, we discovered the interaction between BRCA2 and Mfn present in the outer mitochondrial membrane. Mfn drives fusion of mitochondria in mitochondrial dynamics. Next, we constructed a system for observing intracellular fusion of mitochondria and analyzed the effects of BRCA2 expression and suppression on the fusion function. Furthermore, we have determined the functional domain in BRCA2 that binds to Mfn and regulates the mitochondrial function. We have introduced a breast cancer inducing BRCA2 mutation in the region and are analyzing the modulation of mitochondrial regulation.

Free Research Field

医歯薬学

Academic Significance and Societal Importance of the Research Achievements

ミトコンドリア制御機構におけるBRCA2 の機能解明は、新しい乳がん発症機構の発見に加え、新規治療ターゲットの提案という医学的にも社会的にも要求度の高い成果につながると期待される。