Association between redox regulation by the tumor suppressor gene Drs and malignant transformation of cancer

2021 Fiscal Year Final Research Report

• Project/Area Number: 19K07663
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 50010:Tumor biology-related
• Research Institution: Shiga University of Medical Science
• Principal Investigator: TAMBE YUKIHIRO 滋賀医科大学, 医学部, 准教授 (50283560)
• Project Period (FY): 2019-04-01 – 2022-03-31
• Keywords: 癌抑制遺伝子 / レドックス制御 / Drs / クリプトタンシノン / ピルビン酸脱水素酵素4

Outline of Final Research Achievements

Drs protein is a tumor suppressor gene product closely associated with malignant transformation of human cancers. In this study, we investigated the mechanism by which Drs is involved in intracellular redox regulation, and found that Drs is associated with ROS removal, as Drs knockout cells show an increased sensitivity to hydrogen peroxide. However, this activity is likely to be an indirect effect mediated through the regulation of glucose metabolism by Drs. We also found that inhibitors of PDK4, which act downstream of Drs, have anti-tumour activity and metabolic regulation, suggesting that this mechanism may also contribute to redox regulation by Drs.

Free Research Field

実験病理学

Academic Significance and Societal Importance of the Research Achievements

発癌の過程には多数の癌遺伝子や癌抑制遺伝子が関係しており、その多くが細胞周期制御やシグナル伝達など、細胞の基本的な生理応答に関与することが知られている。一方、我々が新規に報告した癌抑制遺伝子Drsの本来の生理機能は未解明だったが、本研究から糖やアミノ酸、脂質などの代謝調節を通じて抗腫瘍活性を示している仮説が補強された。またその応用として新規PDK4阻害剤クリプトタンシノンの抗腫瘍活性を見出しており、新たな抗癌剤開発につながる可能性が期待される。