Second messenger 2'3'-cyclic GMP-AMP(2'3'-cGAMP):the cell autonomous and non-autonomous roles in cancer progression  

作　　者：Xiao-yu Ma Man-man Chen Ling-hua Meng 

机构地区：[1]Division of Anti-tumor Pharmacology,Shanghai Institute of Materia Medica,Chinese Academy of Sciences,501 Haike Road,Shanghai,201203,China [2]State Key Laboratory of Chemical Biology,Shanghai Institute of Materia Medica,Chinese Academy of Sciences,501 Haike Road,Shanghai,201203,China [3]University of Chinese Academy of Sciences,Beijing,100049,China

出　　处：《Acta Pharmacologica Sinica》2024年第5期890-899,共10页中国药理学报（英文版）

基　　金：supported by State Key Laboratory of Chemical Biology.

摘　　要：Cytosolic double-stranded DNA(dsDNA)is frequently accumulated in cancer cells due to chromosomal instability or exogenous stimulation.Cyclic GMP-AMP synthase(cGAS)acts as a cytosolic DNA sensor,which is activated upon binding to dsDNA to synthesize the crucial second messenger 2’3’-cyclic GMP-AMP(2’3’-cGAMP)that in turn triggers stimulator of interferon genes(STING)signaling.The canonical role of cGAS-cGAMP-STING pathway is essential for innate immunity and viral defense.Recent emerging evidence indicates that 2’3’-cGAMP plays an important role in cancer progression via cell autonomous and non-autonomous mechanisms.Beyond its role as an intracellular messenger to activate STING signaling in tumor cells,2’3’-cGAMP also serves as an immunotransmitter produced by cancer cells to modulate the functions of non-tumor cells especially immune cells in the tumor microenvironment by activating STING signaling.In this review,we summarize the synthesis,transmission,and degradation of 2’3’-cGAMP as well as the dual functions of 2’3’-cGAMP in a STING-dependent manner.Additionally,we discuss the potential therapeutic strategies that harness the cGAMP-mediated antitumor response for cancer therapy.

关 键 词：CDNs 2’3’-cGAMP cGAS-STING tumor microenvironment ENPP1 TREX1 

分 类 号：R730.2[医药卫生—肿瘤]