Claudin-9 (CLDN9) promotes gastric cancer progression by enhancing the glycolysis pathway and facilitating PD-L1 lactylation to suppress CD8+ T cell anti-tumor immunity

This article focuses on the role of Claudin-9 (CLDN9) in the progression of gastric cancer (GC). Key points:

• Distinct glycolysis-related molecular subtypes in GC were identified using TCGA and GEO datasets. CLDN9 was identified as a key gene associated with the glycolytic subtype and prognosis of GC. 

• CLDN9 expression was significantly upregulated in GC patients and cells. Silencing CLDN9 inhibited tumor proliferation, invasion, and metastasis both in vivo and in vitro. 

• Mechanistically, CLDN9 regulated lactate dehydrogenase A (LDHA) expression and promoted glycolytic metabolism through the PI3K/AKT/HIF1α signaling pathway. 

• CLDN9 also facilitated PD-L1 lactylation, which enhanced PD-L1 stability and suppressed CD8+ T cell anti-tumor immunity, contributing to GC progression.