WDR12 Promotes Glucose Metabolism via PFKFB4 Upregulation in Gastric Cancer.

Metabolic reprogramming is a hallmark of gastric cancer (GC); however, the role of transcriptional regulators in modulating glycolysis remains incompletely understood. By integrating proteomic, transcriptomic, and CRISPR-based functional screening datasets, we identified WDR12, a WD40-family protein that is upregulated in GC and associated with poor patient survival. WDR12 silencing suppressed GC cell proliferation and tumor growth in vitro and in vivo and markedly reduced glycolytic flux. Mechanistically, WDR12 interacts with TDP43 and promotes its occupancy at the PFKFB4 promoter, thereby increasing PFKFB4 transcription. Restoration of PFKFB4 expression partially rescued the metabolic and proliferative defects caused by WDR12 knockdown. Together, these findings implicate WDR12 in GC metabolic reprogramming and suggest a potential metabolic vulnerability associated with WDR12-dependent regulation of PFKFB4 through TDP43.