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

TL;DR

This study shows how OASL affects oxaliplatin's ability to trigger cell death in gastric cancer through a specific signaling pathway.

Contribution

The novel finding is that OASL regulates oxaliplatin-induced immunogenic cell death via the cGAS-STING pathway in gastric cancer.

Findings

OASL knockdown enhances oxaliplatin-induced immunogenic cell death in gastric cancer cells.

OASL interacts directly with cGAS, influencing the cGAMP-STING signaling pathway.

Modulating OASL expression could improve oxaliplatin sensitivity in gastric cancer treatment.

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. 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.

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