Stable knockdown of protein kinase CK2-alpha (CK2α) inhibits migration and invasion and induces inactivation of hedgehog signaling pathway in hepatocellular carcinoma Hep G2 cells

Acta Histochem. 2014 Oct;116(8):1501-8. doi: 10.1016/j.acthis.2014.06.001. Epub 2014 Jun 21.

Abstract

Protein kinase CK2-alpha (CK2α), one isoform of the catalytic subunits of serine/threonine kinase CK2, has been indicated to participate in tumorigenesis of various malignancies, including hepatocellular carcinoma (HCC). In the present study, in order to explore the potential role of CK2α in human HCC, we employed short hairpin RNA (shRNA)-mediated RNA interference (RNAi) technology to inhibit the endogenous CK2α expression in HCC cells and established a Hep G2 cell line with stable knockdown of CK2α. Results from wound healing and transwell invasion assays indicated that stable knockdown of CK2α markedly inhibited Hep G2 cell migration and invasion as compared with those transfected with a negative control plasmid. This alteration was accompanied with expression down-regulation of matrix metalloproteinase (MMP)-2, MMP-9, Snail, Slug, Vimentin, and up-regulation of epithelial cadherin (E-cadherin). Moreover, CK2α silencing also induced inactivation of Hedgehog signaling pathway by inhibiting Gli1 and Patched homolog 1 (PTCH1) expressions in HCC cells. Collectively, these results demonstrate that knockdown of CK2α can suppress cell migration and invasion, reduces expression of MMPs, inhibits epithelial-mesenchymal transition (EMT) process and induces inactivation of Hedgehog pathway in HCC cells in vitro. Our study provides in vitro evidence to demonstrate that the pathogenesis of human HCC may be correlated with the high expression of CK2α.

Keywords: CK2α; EMT process; HCC; Hedgehog signaling pathway; MMPs.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Casein Kinase II / genetics
  • Casein Kinase II / metabolism*
  • Cell Movement / genetics
  • Cell Movement / physiology
  • Epithelial-Mesenchymal Transition / genetics
  • Epithelial-Mesenchymal Transition / physiology
  • Hedgehog Proteins / genetics
  • Hedgehog Proteins / metabolism*
  • Hep G2 Cells
  • Humans
  • Matrix Metalloproteinase 2 / genetics
  • Matrix Metalloproteinase 2 / metabolism
  • Matrix Metalloproteinase 9 / genetics
  • Matrix Metalloproteinase 9 / metabolism
  • Signal Transduction / genetics
  • Signal Transduction / physiology
  • Snail Family Transcription Factors
  • Transcription Factors / genetics
  • Transcription Factors / metabolism
  • Vimentin / genetics
  • Vimentin / metabolism

Substances

  • Hedgehog Proteins
  • SNAI1 protein, human
  • Snail Family Transcription Factors
  • Transcription Factors
  • Vimentin
  • Casein Kinase II
  • Matrix Metalloproteinase 2
  • Matrix Metalloproteinase 9