PKM2 regulates hepatocellular carcinoma cell epithelial-mesenchymal transition and migration upon EGFR activation

Asian Pac J Cancer Prev. 2014;15(5):1961-70. doi: 10.7314/apjcp.2014.15.5.1961.

Abstract

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

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Carcinoma, Hepatocellular / genetics*
  • Carcinoma, Hepatocellular / pathology
  • Carrier Proteins / genetics*
  • Cell Line, Tumor
  • Cell Movement / genetics
  • Epidermal Growth Factor / genetics
  • Epithelial-Mesenchymal Transition / genetics*
  • ErbB Receptors / genetics*
  • Hep G2 Cells
  • Humans
  • Liver Neoplasms / genetics*
  • Liver Neoplasms / pathology
  • Lymphoid Enhancer-Binding Factor 1 / genetics
  • Membrane Proteins / genetics*
  • Prognosis
  • TCF Transcription Factors / genetics
  • Thyroid Hormone-Binding Proteins
  • Thyroid Hormones / genetics*
  • Transcription, Genetic / genetics
  • beta Catenin / genetics

Substances

  • Carrier Proteins
  • LEF1 protein, human
  • Lymphoid Enhancer-Binding Factor 1
  • Membrane Proteins
  • TCF Transcription Factors
  • Thyroid Hormones
  • beta Catenin
  • Epidermal Growth Factor
  • EGFR protein, human
  • ErbB Receptors