Silencing of glucose-regulated protein 78 (GRP78) enhances cell migration through the upregulation of vimentin in hepatocellular carcinoma cells

Ann Surg Oncol. 2012 Jul:19 Suppl 3:S572-9. doi: 10.1245/s10434-011-2055-y. Epub 2011 Sep 27.

Abstract

Background: Glucose-regulated protein 78 (GRP78) plays an important role in embryonic development and cancer progression. However, there is little information regarding the regulation of GRP78 in hepatocellular carcinoma (HCC) metastasis.

Methods: We used RNA silencing and cDNA expression vectors to manipulate target gene expression in HCC cells. The transwell migration assay and xCelligence biosensor system were applied to determine the proliferatory and migratory ability of the HCC cells.

Results: In this study, we found that GRP78 silencing enhanced cell migration in both HepJ5 and Mahlavu cells. Overexpressed GRP78 in skHep1 cells suppressed the migratory ability. In the insight mechanism dissection for GRP78-mediated cancer migration, we found that downregulation of GRP78 caused the increase of vimentin expression on HCC cells. Suppressed vimentin expression also decreased the migratory ability on HCC, indicating that vimentin expression levels modulated the cell migratory ability.

Conclusion: We found that silencing GRP78 in HCC cells may enhance cell migration through the increase of vimentin expression.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Carcinoma, Hepatocellular / genetics
  • Carcinoma, Hepatocellular / metabolism*
  • Cell Line, Tumor
  • Cell Movement
  • Cell Proliferation
  • Down-Regulation
  • Endoplasmic Reticulum Chaperone BiP
  • Epithelial-Mesenchymal Transition*
  • Genetic Vectors
  • Heat-Shock Proteins / genetics
  • Heat-Shock Proteins / metabolism*
  • Humans
  • Liver Neoplasms / genetics
  • Liver Neoplasms / metabolism*
  • RNA Interference
  • Up-Regulation
  • Vimentin / genetics
  • Vimentin / metabolism*

Substances

  • Endoplasmic Reticulum Chaperone BiP
  • HSPA5 protein, human
  • Heat-Shock Proteins
  • Vimentin