Zhou Jing, Yang Yi, Fang Yaning, Du Xinyu, Ying Zheye, Rao Chuangzhou
Department of Chemoradiotherapy, Ningbo NO.2 Hospital, Ningbo, Zhejiang 315000, China.
School of Medical Imaging, Hangzhou Medical College, Hangzhou, Zhejiang 310053, China.
Cytokine Growth Factor Rev. 2025 Jul 18. doi: 10.1016/j.cytogfr.2025.07.004.
The cyclic GMP-AMP synthase (cGAS)-stimulator of interferon genes (STING) signaling pathway is an important component of innate immunity, involved in regulating various pathological conditions such as cancer, autoimmune and inflammatory diseases, microbial and parasitic infections. It also regulates various cellular physiological processes, including cytokine production, autophagy, protein synthesis, metabolism, aging, and different types of cell death. Cell death is essential for maintaining homeostasis, promoting tissue repair, and regeneration. Emerging evidence underscores the dynamic interplay between cGAS-STING signaling and cell death, highlighting their relevance in disease pathogenesis and progression. Therefore, elucidating the specific role of the cGAS-STING signaling pathway and associated cell death mechanisms in vivo is critical for targeted disease interventions. This review systematically investigates the mechanistic interactions between the cGAS-STING signaling pathway and cell death modalities, such as autophagy, necroptosis, apoptosis, pyroptosis, ferroptosis, and cuproptosis. Understanding these interactions may provide new therapeutic strategies. We particularly highlight the pathological relevance of cGAS-STING signaling pathway and cell death in human diseases, with a focus on autoimmune disorders, cancer, inflammation, and the impact of organ damage. By clarifying the molecular mechanisms linking cGAS-STING signaling pathway to various cell death modalities and their contributions to disease, we aim to provide a theoretical framework for the rational design of novel therapies targeting this pathway.
环磷酸鸟苷-腺苷合成酶（cGAS）-干扰素基因刺激因子（STING）信号通路是固有免疫的重要组成部分，参与调节多种病理状态，如癌症、自身免疫性疾病、炎症性疾病、微生物和寄生虫感染。它还调节各种细胞生理过程，包括细胞因子产生、自噬、蛋白质合成、代谢、衰老以及不同类型的细胞死亡。细胞死亡对于维持体内平衡、促进组织修复和再生至关重要。新出现的证据强调了cGAS-STING信号与细胞死亡之间的动态相互作用，突出了它们在疾病发病机制和进展中的相关性。因此，阐明cGAS-STING信号通路在体内的具体作用以及相关的细胞死亡机制对于针对性的疾病干预至关重要。本综述系统地研究了cGAS-STING信号通路与细胞死亡方式（如自噬、坏死性凋亡（程序性坏死）、凋亡、焦亡、铁死亡和铜死亡）之间的机制相互作用。了解这些相互作用可能会提供新的治疗策略。我们特别强调了在人类疾病中cGAS-STING信号通路和细胞死亡的病理相关性，重点关注自身免疫性疾病、癌症、炎症以及器官损伤的影响。通过阐明将cGAS-STING信号通路与各种细胞死亡方式联系起来的分子机制及其对疾病的贡献，我们旨在为合理设计针对该通路的新型疗法提供理论框架。
