The relationship between autophagy-related nuclear matrix protein and epigenetic regulation of amino acid metabolism

2022 Fiscal Year Final Research Report

• Project/Area Number: 20K08296
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 53010:Gastroenterology-related
• Research Institution: Juntendo University
• Principal Investigator: Watanabe Sumio 順天堂大学, 医学部, 名誉教授 (20138225)
• Co-Investigator(Kenkyū-buntansha): 山科 俊平 順天堂大学, 医学部, 先任准教授 (30338412)
• Project Period (FY): 2020-04-01 – 2023-03-31
• Keywords: オートファジー / リソソーム / カテプシン / 核マトリクス / 代謝リプログラミング

Outline of Final Research Achievements

In the hepatocarcinoma cell line, cells with enhanced autophagy function had increased cathepsin expression and high proliferative ability. Cells with low-cathepsin expression tended to accumulate lipid droplets. Inducing cathepsin in hepatocytes with steatosis induced lipophagy and mitophagy, reducing oxidative stress. In humanized hepatocytes, proteins involved in metabolic reprogramming accumulated as insoluble nuclear proteins by suppressing cathepsin expression. These results suggest that cathepsin is a regulatory molecule of cell proliferation and lipid metabolism and contributes greatly to cancer metabolism reprogramming. The usefulness of new cathepsin-targeted testing methods and anticancer treatments was suggested.

Free Research Field

肝臓病学

Academic Significance and Societal Importance of the Research Achievements

肝癌は治療法の進歩に伴い治療成績は改善しつつあるが、死亡者数は24,839人（2020年）、５年生存率は35.8 %であり予後が悪い疾患である。肝癌の悪性化の機序は不明な点が多いが、本研究により肝癌悪性化において重要な代謝リプログラミングにリソソーム内蛋白分解酵素カテプシン発現が関与している可能性が示唆された。カテプシンを標的とした新規腫瘍マーカーや抗癌治療法の開発は、肝癌患者の予後改善に結び付く可能性があり社会的に重要な知見が得られた。