PKM2 Regulates Hepatocellular Carcinoma Cell Epithelialmesenchymal Transition and Migration upon EGFR Activation

Abstract

Pyruvate kinase isozyme type M2 (PKM2) was first found in hepatocellular carcinoma (HCC), and itsexpression has been thought to correlate with prognosis. A large number of studies have demonstrated thatepithelial-mesenchymal transition (EMT) is a crucial event in hepatocellular carcinoma (HCC) and associatedmetastasis, resulting in enhanced malignancy of HCC. However, the roles of PKM2 in HCC EMT and metastasisremain largely unknown. The present study aimed to determine the effects of PKM2 in EGF-induced HCCEMT and elucidate the molecular mechanisms in vitro. Our results showed that EGF promoted EMT in HCCcell lines as evidenced by altered morphology, expression of EMT-associated markers, and enhanced invasioncapacity. Furthermore, the present study also revealed that nuclear translocation of PKM2, which is regulatedby the ERK pathway, regulated β-catenin-TCF/LEF-1 transcriptional activity and associated EMT in HCCcell lines. These discoveries provide evidence of novel roles of PKM2 in the progression of HCC and potentialtherapeutic target for advanced cases.