Table 2 cGAS-STING and NF-κB

NF-κB (nuclear factor kappa-light-chain-enhancer of activated B cells) is activated by the cGAS-STING pathway and is an important player in inflammation-induced cancer. NF-κB comprises a group of transcription factors that regulate transcription of a large number of genes involved in many different pathways (e.g. growth and repair) by binding to the κB enhancer. NF-κB can be activated via two main routes, with each of the routes inducing different subunits and establishing different cellular effects [178, 179]. The first activation pathway is the canonical (or classical) pathway, and involves the NF-κB subunits p50 and p65. The second activation pathway is called the non-canonical (or alternative) pathway and involves the NF-κB subunit p52 (derived from p100 processing), as well as the RELB subunit. While canonical NF-κB activation is strong and transient, non-canonical NF-κB activation is slower and more often constitutive [179]. Canonical NF-κB activity includes the secretion of many inflammatory compounds, such as TNF and interleukins [178]. Non-canonical NF-κB activity is associated with lymphoid organ development, autoimmune T-cell removal, bone metabolism and B-cell maturation [179]. The important role of NF-κB in cancer promotion has been shown in two pioneering papers looking into Colitis-Associated Cancer and Hepatocellular carcinoma, respectively [180, 181]. NF-κB has an impact on many different pathways, and has been found to promote proliferation, angiogenesis, EMT, matrix degradation, and sustained inflammation [178, 182,183,184,185,186]. Moreover, inhibition of NF-κB induces antitumour effects and has been found to inhibit metastasis [187, 188]. As NF-κB is activated by cGAS-STING (among other pathways), it seems plausible that cGAS-STING-mediated NF-κB activation can promote metastasis.