Mechanistic insights into SUMOylation and its role in cancer pathogenesis: bridging oncogenesis, immunity, and therapeutic opportunities.

IF 4.7 2区医学 Q2 IMMUNOLOGY

International immunopharmacology Pub Date : 2025-10-30 Epub Date: 2025-08-09 DOI:10.1016/j.intimp.2025.115332

Wei Qu, Jinning Gu, Shanshan Liu, Wen Xiao, Yanwei Li

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引用次数: 0

Abstract

SUMOylation is a post-translational modification mediated by SUMO proteins, a family of small ubiquitin-like biological macromolecules that covalently attach to specific lysine residues in target proteins. This modification regulates various macromolecular functions, including transcriptional control, subcellular localization, DNA repair, and cell cycle progression. Recent advances have unveiled the multifaceted roles of SUMOylation in cancer pathogenesis, encompassing oncogenesis, immune modulation, and therapeutic resistance. This review details the molecular mechanisms of SUMOylation and its deregulation in tumor development, highlighting its role in genomic stability, transcriptional regulation, and signal transduction, key elements in tumor progression and metastasis. Additionally, the role of SUMOylation in the tumor microenvironment (TME) and immune evasion is explored, with emphasis on its interactions with immune checkpoint pathways and inflammatory signaling. Insights into SUMOylation's involvement in treatment resistance, particularly chemoresistance and radioresistance, are presented alongside an overview of emerging therapeutic strategies targeting this pathway. The potential of SUMOylation as a diagnostic and prognostic biomarker is also discussed, underscoring its translational significance in personalized oncology. By bridging oncogenesis, immune regulation, and therapy, this review aims to unify the current understanding of SUMOylation's role in cancer. Targeting SUMOylation presents a promising avenue for developing innovative cancer therapies that address immune modulation and treatment resistance. This review provides a roadmap for future research, fostering advancements in SUMOylation biology and its therapeutic applications in oncology.

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SUMOylation的机制及其在癌症发病机制中的作用：桥接肿瘤发生、免疫和治疗机会。

SUMO蛋白是一类类似泛素的小生物大分子，共价附着在靶蛋白的特定赖氨酸残基上。这种修饰调节各种大分子功能，包括转录控制、亚细胞定位、DNA修复和细胞周期进程。最近的进展揭示了SUMOylation在癌症发病机制中的多方面作用，包括肿瘤发生、免疫调节和治疗耐药性。本文详细介绍了sumo酰化的分子机制及其在肿瘤发展中的调控作用，重点介绍了sumo酰化在基因组稳定性、转录调控和信号转导中的作用，以及sumo酰化在肿瘤进展和转移中的关键作用。此外，SUMOylation在肿瘤微环境（TME）和免疫逃避中的作用被探索，重点是它与免疫检查点途径和炎症信号的相互作用。深入了解SUMOylation参与治疗耐药，特别是化疗耐药和放射耐药，并概述了针对该途径的新兴治疗策略。本文还讨论了SUMOylation作为诊断和预后生物标志物的潜力，强调了其在个性化肿瘤学中的转化意义。通过连接肿瘤发生、免疫调节和治疗，本综述旨在统一目前对SUMOylation在癌症中的作用的理解。靶向SUMOylation为开发解决免疫调节和治疗耐药性的创新癌症疗法提供了一条有希望的途径。这篇综述为未来的研究提供了一个路线图，促进summoylation生物学及其在肿瘤治疗中的应用。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

International immunopharmacology 医学-免疫学

CiteScore

8.40

自引率

3.60%

发文量

935

审稿时长

53 days

期刊介绍： International Immunopharmacology is the primary vehicle for the publication of original research papers pertinent to the overlapping areas of immunology, pharmacology, cytokine biology, immunotherapy, immunopathology and immunotoxicology. Review articles that encompass these subjects are also welcome. The subject material appropriate for submission includes: • Clinical studies employing immunotherapy of any type including the use of: bacterial and chemical agents; thymic hormones, interferon, lymphokines, etc., in transplantation and diseases such as cancer, immunodeficiency, chronic infection and allergic, inflammatory or autoimmune disorders. • Studies on the mechanisms of action of these agents for specific parameters of immune competence as well as the overall clinical state. • Pre-clinical animal studies and in vitro studies on mechanisms of action with immunopotentiators, immunomodulators, immunoadjuvants and other pharmacological agents active on cells participating in immune or allergic responses. • Pharmacological compounds, microbial products and toxicological agents that affect the lymphoid system, and their mechanisms of action. • Agents that activate genes or modify transcription and translation within the immune response. • Substances activated, generated, or released through immunologic or related pathways that are pharmacologically active. • Production, function and regulation of cytokines and their receptors. • Classical pharmacological studies on the effects of chemokines and bioactive factors released during immunological reactions.