No Longer A One-Trick Pony: STING Signaling Activity Beyond Interferon

Stimulator of interferon genes (STING) plays an important role in infection, autoimmune disease and cancer. STING-mediated type I interferon (IFN) signaling is well recognized and extensively studied. Several IFN-independent activities of STING were also discovered in recent years and their physiological importance has begun to be appreciated. Here, we review recent advance in the evolutionary origin and molecular mechanisms of STING-mediated IFN-independent activities. New insights from these studies suggest that STING is not just a simple IFN-producing machine, rather, it functions as a hub that converts multiple environmental cues into diverse cellular responses. This expanded view of STING biology should guide future clinical testing of STING agonists in cancer and treatment of STING-associated human diseases.