Exogenous DNA enhances DUOX2 expression and function in human pancreatic cancer cells by activating the cGAS-STING signaling pathway.

ABSTRACT: Pro-inflammatory cytokines upregulate the expression of the H₂O₂-producing NADPH oxidase dual oxidase 2 (DUOX2)² which, when elevated, adversely affects survival from pancreatic ductal adenocarcinoma (PDAC). Because the cGAS-STING pathway is known to initiate pro-inflammatory cytokine expression following uptake of exogenous DNA, we examined whether activation of cGAS-STING could play a role in the generation of reactive oxygen species by PDAC cells. Here, we found that a variety of exogenous DNA species markedly increased the production of cGAMP, the phosphorylation of TBK1 and IRF3, and the translocation of phosphorylated IRF3 into the nucleus, leading to a significant, IRF3-dependent enhancement of DUOX2 expression, and a significant flux of H₂

SUBMITTER: Wang SL 

PROVIDER: S-EPMC10527782 | biostudies-literature | 2023 Aug

REPOSITORIES: biostudies-literature