<br>氧化应激通过 RNF25 介导的 E-钙粘蛋白降解促进肝癌转移,Advanced Science

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氧化应激通过 RNF25 介导的 E-钙粘蛋白降解促进肝癌转移
Advanced Science ( IF 14.3 ) Pub Date : 2024-01-29 , DOI: 10.1002/advs.202306929
Zhao Huang ₁ , Li Zhou ₂ , Jiufei Duan ₁ , Siyuan Qin ₁ , Jingwen Jiang ₃ , Haining Chen ₄ , Kui Wang ₅ , Rui Liu ₆ , Minlan Yuan ₇ , Xiangdong Tang ₈ , Edouard C Nice ₉ , Yuquan Wei ₁ , Wei Zhang _{10,

11} , Canhua Huang _{1,

10}

Affiliation

Department of Biotherapy, Cancer Center and State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, 610041, China.
Key Laboratory of Molecular Biology for Infectious Diseases (Ministry of Education), Institute for Viral Hepatitis, Department of Infectious Diseases, The Second Affiliated Hospital, Chongqing Medical University, Chongqing, 400016, China.
West China School of Public Health and West China Fourth Hospital, Sichuan University, Chengdu, 610041, China.
Colorectal Cancer Center, Department of General Surgery, West China Hospital, Sichuan University, Chengdu, 610041, China.
West China School of Basic Medical Sciences & Forensic Medicine, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, 610041, China.
State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Diseases, Research Unit of Oral Carcinogenesis and Management, Chinese Academy of Medical Sciences, West China Hospital of Stomatology, Sichuan University, Chengdu, 610041, China.
Mental Health Center and Psychiatric Laboratory, The State Key Laboratory of Biotherapy, West China Biomedical Big Data Center, West China Hospital of Sichuan University, Chengdu, 610041, China.
Sleep Medicine Center, Department of Respiratory and Critical Care Medicine, Mental Health Center, Translational Neuroscience Center, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, 610041, China.
Department of Biochemistry and Molecular Biology, Monash University, Clayton, VIC, 3167, Australia.
Frontiers Medical Center, Tianfu Jincheng Laboratory, Chengdu, 610212, China.
Medical Big Data Center, Sichuan University, Chengdu, 610041, China.

肿瘤转移需要 E-钙粘蛋白 (ECAD) 的损失。在肝细胞癌 (HCC) 转移中发现了 ECAD 响应氧化应激的蛋白质降解，并且与通常所知的转录抑制无关。从机制上讲，蛋白激酶 A (PKA) 通过其 β 催化亚基 (PRKACB) Cys200 和 Cys344 处的氧化还原修饰来感知氧化应激。 PKA 激酶活性的激活随后诱导 RNF25 Ser450 磷酸化，从而启动 RNF25 催化的 ECAD 降解。从功能上讲，RNF25 抑制可诱导 ECAD 蛋白表达，并在体外和体内抑制 HCC 转移。总而言之，这些结果表明 RNF25 是 ECAD 蛋白质周转的关键调节因子，而 PKA 是实现该过程所需的氧化还原传感器。这项研究提供了一些关于氧化应激诱导的 ECAD 降解如何促进 HCC 肿瘤转移的机制见解。

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更新日期：2024-01-29

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