DEK recruits KAT6A regulate H3K27ac/c-myc axis to drive enhanced glycolysis and immune escape in gastric cancer.

Increased glycolytic activity and immune evasion mechanisms in gastric cancer represent significant impediments to therapeutic advancements. In this study, KAT6A was strikingly upregulated in both gastric cancer tissues and cell lines and was significantly associated with malignant phenotypes and shorter survival periods. We have demonstrated that KAT6A upregulates acetylated histone levels, thereby increasing the transcriptional activity of genes, including HK2, PDL1, and CD47. This consequently promotes elevated glycolytic flux and facilitates immune evasion. Notably, for the first time, we discovered that DEK plays a crucial synergistic role in the activation of H3K27ac by KAT6A and that the knockout of DEK can rescue the related effects of overexpressing KAT6A. Moreover, knockdown of KAT6A and DEK suppressed malignant phenotypes in gastric cancer cells, including proliferation, invasion, and migration, while enhancing macrophage phagocytic function and CD8+ T-cell activity. Moreover, combined treatment with KAT6A inhibition and an anti-CD47 agent has excellent therapeutic efficacy. These findings reveal the regulatory mechanism through which KAT6A and DEK cooperate to regulate glycolysis levels and immune escape in gastric cancer and provide therapeutic targets and promising treatment strategies for tumor intervention.