Ochratoxin A Induces Epithelial Mesenchymal Transition of Human Gastric Epithelium GES‐1 Cells via the PKM2‐Dependent Glycolytic Metabolism

Ochratoxin A (OTA), a potent mycotoxin with well‐documented carcinogenic potential, facilitates tumor progression by triggering epithelial–mesenchymal transition (EMT). Nevertheless, the precise molecular pathways governing this phenomenon remain elusive. In this investigation, we sought to delineate OTA's involvement in EMT and explore its association with glycolytic metabolism and pyruvate kinase M2 (PKM2) regulation in human gastric epithelial GES‐1 cells. Utilizing pharmacological interventions, RNA interference, and comprehensive molecular analyses, we observed that OTA exposure induced a phenotypic shift in GES‐1 cells, characterized by a transition from cobblestone‐like morphology to spindle‐shaped appearance. This morphological transformation correlated with downregulation of the epithelial marker E‐cadherin and concomitant upregulation of mesenchymal markers N‐cadherin and vimentin, collectively confirming EMT induction. The glycolysis inhibitor 2‐deoxy‐ d ‐glucose (2DG) and PKM2 siRNA both significantly reversed these OTA‐induced changes, suggesting a critical role for glycolysis and PKM2 in the OTA‐mediated EMT process. Mechanistically, 2DG inhibited glycolysis, while PKM2 siRNA disrupted the metabolic reprogramming required for EMT. These findings underscore the importance of glycolytic metabolism and PKM2 in OTA‐induced EMT and provide a rationale for targeting these pathways in the treatment of OTA‐associated malignancies.