Promotes Glucose Metabolism viaUpregulation in Gastric Cancer

Source: PubMed Central Open Access, NCBI / U.S. National Library of Medicine

ABSTRACT 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.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 thepromoter, thereby increasingtranscription. Restoration ofexpression partially rescued the metabolic and proliferative defects caused byknockdown. Together, these findings implicatein GC metabolic reprogramming and suggest a potential metabolic vulnerability associated with‐dependent regulation ofthrough TDP43. WDR12 promotes glucose metabolism and tumor growth in GC. Mechanistically, WDR12 interacts with TDP43 and appears to enhance PFKFB4 expression, thereby promoting glucose metabolism. graphical