Role of micronucleus-activated cGAS-STING signaling in antitumor immunity
10.3724/zdxbyxb-2023-0485
- VernacularTitle:微核激活cGAS-STING信号通路的机制及其肿瘤免疫功能
- Author:
Qin SHEN
1
;
Pinglong XU
;
Chen MEI
Author Information
1. 浙江大学生命科学研究院,浙江 杭州 310058
- Keywords:
cGAS-STING signaling;
Chromosomal instability;
Micronucleus;
Tumor immunology;
Review
- From:
Journal of Zhejiang University. Medical sciences
2024;53(1):25-34
- CountryChina
- Language:Chinese
-
Abstract:
Cyclic guanosine monophosphate-adenosine monophosphate synthase(cGAS)-stimulator of interferon genes(STING)signaling is a significant component of the innate immune system and functions as a vital sentinel mechanism to monitor cellular and tissue aberrations in microbial invasion and organ injury.cGAS,a cytosolic DNA sensor,is specialized in recognizing abnormally localized cytoplasmic double-stranded DNA(dsDNA)and catalyzes the formation of a second messenger cyclic-GMP-AMP(cGAMP),which initiates a cascade of type Ⅰ interferon and inflammatory responses mediated by STING.Micronucleus,a byproduct of chromosomal missegregation during anaphase,is also a significant contributor to cytoplasmic dsDNA.These unstable subcellular structures are susceptible to irreversible nuclear envelope rupture,exposing genomic dsDNA to the cytoplasm,which potently recruits cGAS and activates STING-mediated innate immune signaling and its downstream activities,including type Ⅰ interferon and classical nuclear factor-κB(NF-κB)signaling pathways lead to senescence,apoptosis,autophagy activating anti-cancer immunity or directly killing tumor cells.However,sustained STING activation-induced endoplasmic reticulum stress,activated chronic type Ⅰinterferon and nonclassical NF-κB signaling pathways remodel immunosuppressive tumor microenvironment,leading to immune evasion and facilitating tumor metastasis.Therefore,activated cGAS-STING signaling plays a dual role of suppressing or facilitating tumor growth in tumorigenesis and therapy.This review elaborates on research advances in mechanisms of micronucleus inducing activation of cGAS-STING signaling and its implications in tumorigenesis and therapeutic strategies of malignant tumors.
