Effect of OASL on OXA-induced immunogenic cell death in gastric cancer via cGAS-STING pathway

Abstract

This study investigates the role of 2-5 oligoadenylate synthetase-like (OASL) in Oxaliplatin (OXA)-induced immunogenic cell death (ICD) in Gastric cancer (GC) cells through the cGAS-STING signaling pathway. Knockdown of OASL enhanced ICD expression, while overexpression had the opposite effect. RNA sequencing of OASL-knockdown and control GC cells treated with OXA revealed significant enrichment of the second messenger signaling pathway (cGAMP). cGAMP could directly activate STING as a second messenger, and cGAS was a key synthetic enzyme upstream of cGAMP. Next, the role of OASL in OXA-induced ICD in GC cells was validated through the cGAS-STING signaling pathway. The Co-IP and immunofluorescence results confirmed that the OASL and cGAS proteins can bind directly. Further research validated these findings in vivo. Results show that OASL regulates OXA-induced ICD in GC cells via the cGAS-STING pathway, impacting chemosensitivity. The findings suggest new targets and strategies for improving GC therapy by modulating OASL expression to enhance OXA sensitivity through immunogenic mechanisms.