Targeting of the mitochondria-ER-tethering protein PDZD8 for osteosarcoma treatment

2021 Fiscal Year Final Research Report

• Project/Area Number: 20K18007
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 56020:Orthopedics-related
• Research Institution: Nara Medical University
• Principal Investigator: Kishi Shingo 奈良県立医科大学, 医学部, 助教 (50790341)
• Project Period (FY): 2020-04-01 – 2022-03-31
• Keywords: ミトコンドリア繋留分子 / PDZD8 / 骨肉腫 / 活性酸素 / 鉄 / スニチニブ / プテロスチルベン

Outline of Final Research Achievements

Mitochondria-associated membranes (MAMs) have attracted much attention which tethers mitochondria and endoplasmic reticulum (ER) to influence substance transfer and metabolism between the two. In this study, we examined the function of PDZD8 among MAMs, suggesting that PDZD8 protein is expressed in a tumor-specific manner, regulating mitochondrial iron metabolism and suppressing ROS production. Inhibition of PDZD8 promoted the antitumor effects of anticancer drugs and pterostilbene, which inhibits F1F0-ATPase, from increased ROS production. Sunitinib might suppress PDZD8 as its off target.

Free Research Field

がん生物学

Academic Significance and Societal Importance of the Research Achievements

PDZD8が腫瘍特異的に発現し、その抑制が抗がん剤などの抗腫瘍効果を促進したことは、PDZD8ががん治療における新たな分子標的となることが考えられる。とくに、SunitinibはPDZD8をoff targetとして抑制したことは、今後のPDZD8のシグナル経路の解明の手掛かりとなるとともに、PDZD8を標的とする創薬に繋がる知見と考えられる。