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journal article·2024-04Open access

Oxidative Stress Promotes Liver Cancer Metastasis via RNF25‐Mediated E‐Cadherin Protein Degradation

Zhao Huang, Li Zhou, Jiufei Duan, Siyuan Qin, Jingwen Jiang, Haining Chen, Kui Wang, Rui Liu, Minlan Yuan, Xiangdong Tang, Edouard C. Nice, Yuquan Wei, Wei Zhang, Canhua Huang

Advanced Science· Volume 11· Issue 13
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Source abstract

Abstract

Abstract Loss of E‐cadherin (ECAD) is required in tumor metastasis. Protein degradation of ECAD in response to oxidative stress is found in metastasis of hepatocellular carcinoma (HCC) and is independent of transcriptional repression as usually known. Mechanistically, protein kinase A (PKA) senses oxidative stress by redox modification in its β catalytic subunit (PRKACB) at Cys200 and Cys344. The activation of PKA kinase activity subsequently induces RNF25 phosphorylation at Ser450 to initiate RNF25‐catalyzed degradation of ECAD. Functionally, RNF25 repression induces ECAD protein expression and inhibits HCC metastasis in vitro and in vivo. Altogether, these results indicate that RNF25 is a critical regulator of ECAD protein turnover, and PKA is a necessary redox sensor to enable this process. This study provides some mechanistic insight into how oxidative stress‐induced ECAD degradation promotes tumor metastasis of HCC.
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Research context

Catalysis & surfaces

OpenAlex topics: Genomics, phytochemicals, and oxidative stress · Endoplasmic Reticulum Stress and Disease · Sirtuins and Resveratrol in Medicine

SciVX discovery tags are terminology-based. OpenAlex topics are source-provided classifications.

Affiliations

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

Funding

National Key Research and Development Program of China · Ministry of Science and Technology of the People's Republic of China · National Natural Science Foundation of China

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