Decoding STING's roles in cancer: immunity, pain, dormancy, and autophagy.

IF 3.7 2区 生物学 Q3 CELL BIOLOGY
Molecular and Cellular Biochemistry Pub Date : 2025-08-01 Epub Date: 2025-04-24 DOI:10.1007/s11010-025-05281-4
Huan-Xin Lin, Ya-Ling Tang, Xin-Hua Liang
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引用次数: 0

Abstract

Stimulator of interferon genes (STING) is ubiquitously localized in the endoplasmic reticulum of diverse cell types, serving as a cornerstone of the cyclic GMP-AMP synthase (cGAS)-STING signaling pathway, which is critical for detecting cytosolic DNA and initiating innate immune responses. Conventionally, researchers have characterized STING as a tumor suppressor; however, emerging evidence indicates that activating STING may also facilitate tumor progression. Notably, the tumor-suppressive and tumor-promoting effects mediated by STING are highly context dependent and influenced by specific tumor types and stages. Beyond its central role in immune defense, the STING signaling pathway regulates various physiological and pathological processes within cells. Dormant tumor cells, for instance, can adjust their STING expression to evade immune detection and clearance. Additionally, STING-induced autophagy functions as a negative regulator of STING, establishing a reciprocal interplay that impacts both innate immunity and antitumor immunity. Furthermore, STING activation can simultaneously stimulate the production of proinflammatory and anti-inflammatory cytokines, underscoring its dualistic impact on cancer pain modulation. Therefore, a nuanced understanding of STING's immunoregulatory and alternative roles in antitumor immunity is essential for effectively designing STING-targeted cancer therapies. This review comprehensively analyzes STING's structure and function, systematically elucidating its mechanisms and roles in antitumor immunity, dormancy, autophagy, and cancer pain modulation. By integrating current insights, this work aims to establish a robust theoretical foundation for advancing the development and clinical implementation of STING-targeted cancer therapies.

解码STING在癌症中的作用:免疫、疼痛、休眠和自噬。
干扰素刺激因子基因(STING)普遍存在于多种细胞类型的内质网中,是环GMP-AMP合成酶(cGAS)-STING信号通路的基石,对于检测胞质DNA和启动先天免疫应答至关重要。传统上,研究人员将STING描述为肿瘤抑制因子;然而,新出现的证据表明,激活STING也可能促进肿瘤进展。值得注意的是,STING介导的肿瘤抑制和肿瘤促进作用高度依赖于特定的肿瘤类型和分期。除了在免疫防御中发挥核心作用外,STING信号通路还调节细胞内的各种生理和病理过程。例如,休眠的肿瘤细胞可以调节其STING表达以逃避免疫检测和清除。此外,STING诱导的自噬作为STING的负调节因子,建立了影响先天免疫和抗肿瘤免疫的相互作用。此外,STING激活可以同时刺激促炎和抗炎细胞因子的产生,强调其对癌症疼痛调节的双重影响。因此,深入了解STING在抗肿瘤免疫中的免疫调节和替代作用对于有效设计STING靶向癌症治疗至关重要。本文综合分析了STING的结构和功能,系统阐述了其在抗肿瘤免疫、休眠、自噬和癌痛调节等方面的机制和作用。通过整合目前的见解,本研究旨在为推进sting靶向癌症治疗的开发和临床实施奠定坚实的理论基础。
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
Molecular and Cellular Biochemistry
Molecular and Cellular Biochemistry 生物-细胞生物学
CiteScore
8.30
自引率
2.30%
发文量
293
审稿时长
1.7 months
期刊介绍: Molecular and Cellular Biochemistry: An International Journal for Chemical Biology in Health and Disease publishes original research papers and short communications in all areas of the biochemical sciences, emphasizing novel findings relevant to the biochemical basis of cellular function and disease processes, as well as the mechanics of action of hormones and chemical agents. Coverage includes membrane transport, receptor mechanism, immune response, secretory processes, and cytoskeletal function, as well as biochemical structure-function relationships in the cell. In addition to the reports of original research, the journal publishes state of the art reviews. Specific subjects covered by Molecular and Cellular Biochemistry include cellular metabolism, cellular pathophysiology, enzymology, ion transport, lipid biochemistry, membrane biochemistry, molecular biology, nuclear structure and function, and protein chemistry.
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