Figure 4.

The cGAS–STING pathway in cancer. (A) In certain cancers, the cGAS–STING pathway induces autophagy-dependent cell death to limit the transformation of normal cells into cancerous cells. (B) The cGAS–STING pathway inhibits the growth of certain cancer cells by inducing the secretion of anti-proliferative molecules that promote senescence. (C) In specific cancers, 2′3′-cGAMP from the cancer cells enters the cytosol of DCs through the gap junction or TEX, activating STING to produce type-I IFN. The type-I IFN from the DCs then cross-primes CD8⁺ T cells to eliminate tumorigenic cells. (D) Within some cancers, 2′3′-cGAMP from the cancer cells is transferred into non-tumor bystander cells via the gap junction and activates STING, resulting in the recruitment of NK cells to restrain tumor growth. (E) In the case of certain cancer cells, chemical treatments cause the introduction of damaged DNA into the cytosol. This damaged DNA further engages the cGAS–STING pathway, inducing the secretion of DMBA to facilitate inflammation and maintain the tumor microenvironment. (F) STING activation also occurs after 2′3′-cGAMP from specific cancer cells are trafficked to astrocytes via the gap junction. The activated STING in the astrocytes promotes STAT1 and NF-κB production, further facilitating the development of metastatic cancer cells. (G) The loss of function of cGAS or STING leads to immunosuppression in cancer cells due to the hindered production of type-I IFN and other cytokines. Abbreviations: TEX, tumor-derived exosomes; DCs, infiltrating dendritic cells; NK cells, natural killer cells; DMBA, 7, 12-dimethylbenz(a)anthracene; cGAS–STING, cyclic GMP-AMP synthase-stimulator of interferon genes; 2′3′-cGAMP, 2′3′-cGMP-AMP; type-I IFN, type-I interferon.