PKM2Regulates Cell Motility Through EGF/EGFR And TGFβ/TGFβR Signal Pathways In Hepatocellular Carcinoma Cells

Backgrounds and Aims:The M2splice isoform of pyruvate kinase (PKM2) is important for cancer metabolismand tumour growth. PKM2has been shown to be essential for aerobic glycolysis intumors (Warburg effect). Another findings reveal a novel role for PKM2as atranscriptional coactivator and promoted cell proliferation. But the function of PKM2on cell motility and invasion was reported as a inhibitory role. So we aimed to explorethe role of PKM2in hepatocellular carcinoma cells and define the biologicalmechanisms for PKM2in regulating the cell motility and invasion.Methods: We employed stable transfection with short hairpin RNA to stably silencethe expression of PKM2in the HepG2and Huh-7hepatocellular carcinoma cell lines.The effects of PKM2in vitro were determined by assessing cell proliferation,migration and invasion. And the related gene expression which regulated by PKM2were explored through mRNA sequencing methods.Results: We found the decreased proliferation of hepatocellular carcinoma cellsafter PKM2interference, however the cell metastasis was enhanced when stimulatedby EGF. Our results indicate that the knockdown of PKM2decreased the expressionof E-cadherin and enhanced the EGF/EGFR signaling pathway in the hepatocellularcarcinoma cell lines HepG2and Huh-7. These changes were due to the activation ofTGFb signaling pathway after PKM2knock-down. We also found that the expressionof TGFBRII was increased and the phosphorylation of Smad2/3was enhanced.Conclusion: PKM2may play different roles in modulating proliferation andmetastasis of hepatocellular carcinoma cells. The results of our study reveal animportant link between PKM2and TGF-β pathway during EGFR-stimulatedhepatocellular carcinoma cell motility and invasion. This finding would be affect theguidance of future targeted therapy.