{"title":"Decoding STING's roles in cancer: immunity, pain, dormancy, and autophagy.","authors":"Huan-Xin Lin, Ya-Ling Tang, Xin-Hua Liang","doi":"10.1007/s11010-025-05281-4","DOIUrl":null,"url":null,"abstract":"<p><p>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.</p>","PeriodicalId":18724,"journal":{"name":"Molecular and Cellular Biochemistry","volume":" ","pages":"4697-4723"},"PeriodicalIF":3.7000,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Molecular and Cellular Biochemistry","FirstCategoryId":"99","ListUrlMain":"https://doi.org/10.1007/s11010-025-05281-4","RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2025/4/24 0:00:00","PubModel":"Epub","JCR":"Q3","JCRName":"CELL BIOLOGY","Score":null,"Total":0}
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.
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.