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The ISGylation tapestry in cancer: weaving phenotypic plasticity through multidimensional regulatory looms

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机构: [1]Urology & Nephrology Center, Department of Urology, Affiliated People’s Hospital, Zhejiang Provincial People’s Hospital, Hangzhou Medical College, Hangzhou, Zhejiang, China. [2]Department of Urology, Institute of Urology, West China Hospital, Sichuan University, Chengdu 610041, China. [3]Division of Surgery & Interventional Science, University College London, London W1W 7TS, UK. [4]Department of Rehabilitation, The Affiliated Hospital of Southwest Medical University, Luzhou 646000, People’s Republic of China. [5]Chengdu Basebio Company, Chengdu, China. [6]Faculty of Health and Life Sciences, University of Bristol, Bristol BS8 1TD, UK. [7]Basic and Translational Cancer Research Group, Department of Pharmacology and Therapeutics, College of Medicine, University of Nigeria, Nsukka, Enugu, Nigeria. [8]Department of Urological Surgery, Daping Hospital, Army Medical Center of PLA, Army Medical University, Chongqing, China. [9]Clinical Medicine Research Institute, Zhejiang Provincial People’s Hospital of Hangzhou Medical College, Hangzhou, China. [10]Department of Comparative Pathobiology, College of Veterinary Medicine, Purdue University, West Lafayette, IN 47907, USA. [11]Purdue Institute for Cancer Research, Purdue University, West Lafayette, IN 47907, USA.
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关键词: Post-translational modification ISGylation Tumor microenvironment Immune evasion Drug resistance

摘要:
Post-translational modification is an important mechanism for regulating protein function and cell signaling networks. Among these modifications, ISGylation is a ubiquitin-like modification regulated by ISG15. In this review, we explore the role of ISGylation in a variety of related phenotypes in the tumor context, including apoptosis regulation, autophagy regulation, immune escape, metabolic reprogramming, cancer stem cell maintenance, and DNA damage repair. ISGylation plays a dual role in apoptosis, promoting either pro-survival or pro-death pathways depending on contexts. It also regulates autophagy by promoting tumor adaptation or by regulating immune responses. Moreover, ISGylation contributes to the immune escape mechanism by regulating the stability of PD-L1 and immune cell infiltration. In addition, ISGylation is involved in metabolic reprogramming, supporting tumor growth and therapeutic resistance by regulating key metabolic pathways. It also plays a key role in maintaining the properties of cancer stem cells by stabilizing essential metabolic and signaling proteins. In sum, this review examines the functions and mechanisms of ISG15 and ISGylation in various tumor-associated phenotypes, enhancing our understanding of their role in tumorigenesis and disease progression.© 2025. The Author(s).

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出版当年[2025]版:
大类 | 1 区 生物学
小类 | 2 区 生化与分子生物学 2 区 细胞生物学
最新[2025]版:
大类 | 1 区 生物学
小类 | 2 区 生化与分子生物学 2 区 细胞生物学
第一作者:
第一作者机构: [1]Urology & Nephrology Center, Department of Urology, Affiliated People’s Hospital, Zhejiang Provincial People’s Hospital, Hangzhou Medical College, Hangzhou, Zhejiang, China. [2]Department of Urology, Institute of Urology, West China Hospital, Sichuan University, Chengdu 610041, China. [3]Division of Surgery & Interventional Science, University College London, London W1W 7TS, UK.
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通讯机构: [1]Urology & Nephrology Center, Department of Urology, Affiliated People’s Hospital, Zhejiang Provincial People’s Hospital, Hangzhou Medical College, Hangzhou, Zhejiang, China. [3]Division of Surgery & Interventional Science, University College London, London W1W 7TS, UK.
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