STING Promotes Homeostasis via Regulation of Cell Proliferation and Chromosomal Stability

Given the integral role of Stimulatorof interferon genes( STING, TMEM173) in the innate immune response, its loss or impairment in cancer is thought to primarily affect antitumor immunity. Here we demonstrate a role for STINGin the maintenance of cellular homeostasisthrough regulation of the cell cycle. Depletion of STINGin human and murine cancer cells and tumors resulted in increased proliferation compared to wild-type controls. Microarray analysis revealed genes involved in cell cycleregulation are differentially expressed in STINGko compared to WT MEFs. STING-mediated regulation of the cell cycleconverged on NF-κB- and p53-driven activation of p21. The absence of STINGled to premature activation of cyclin-dependent kinase 1(CDK1), early onset S phase and mitosis, and increased chromosome instability, which was enhanced by ionizing radiation (IR). These results suggest a pivotal role for STINGin maintaining cellular homeostasisand response to genotoxic stress.