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

作者：Lingling Zhang, Yi Liu, Haiying Yang, Luguang Liu, Wang Longgang, Jie Chai, Weizhu Zhao, Dong Sun · 发表于：Cell Death Discovery · 年份：2025 · DOI：10.1038/s41420-025-02850-w · 被引用次数：3 · 研究领域：interferon and immune responses、Ubiquitin and proteasome pathways、NF-κB Signaling Pathways

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. mRNA sequencing of OASL-knockdown and control GC cells treated with OXA revealed significant enrichment of the cGAMP-mediated second messenger signaling pathway. cGAS synthesizes the second messenger molecule cGAMP, which directly activated STING. To clarify the mechanism, the role of OASL in OXA-induced ICD in GC cells was validated as mediated by the cGAS-STING signaling pathway. The Co-IP and immunofluorescence results confirmed that the OASL and cGAS proteins can bind directly. Further research using an in vivo mouse model validated these findings. 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 ICD mechanisms.