Fig. 4

Regulation of cGAS-STING pathway in tumor promotion. The cGAS-STING pathway could exert its pro-tumor role in metastatic tumor settings. STING functions as a platform for different tumorigenic programs. High chromosome instability (CIN) tumors generated micronuclei, and its rupture could release DNA to the cytosol, enhancing the sense of cGAS-STING. Low tumor antigenicity and cytoplasmic chromatin chronic activation contribute to malignancy formation, through the activation of the cGAS-STING pathway. Chronic activation could also downregulate the expression of type I IFNs, upregulate noncanonical NF-κB signaling, and promote tumor metastasis. Indoleamine 2,3-dioxygenase (IDO) and anti-inflammatory cytokines released from the tumor induces the formation of an immunosuppressive TME. STING may also promote immune evasion and tumor metastasis by PD-L1 upregulation and autophagy induction. In addition, cGAMP, particularly, was reported to transfer from the tumor cells through gap junctions to astrocytes, promoting NF-κB and IFN signaling and inducing brain metastasis ultimately. Abbreviations: cGAMP, 2′,3′-cyclic GMP-AMP; IDO, indoleamine 2,3-dioxygenase; PD-L1, programmed death-ligand 1; TME, tumor microenvironment