Glucose-regulated protein 78 (GRP78) silencing enhances cell migration but does not influence cell proliferation in hepatocellular carcinoma

Ann Surg Oncol. 2010 Jun;17(6):1703-9. doi: 10.1245/s10434-010-0912-8. Epub 2010 Jan 20.

Abstract

Background: GRP78 plays an essential role in embryonic development and in the therapeutic treatment and progression of cancer. However, little is known about the role of GRP78 in hepatocellular carcinoma (HCC).

Methods: In this study, we characterized five different HCC cell lines to examine GRP78 expression patterns and found that only HepJ5 cells ectopically overexpress GRP78. We knocked down GRP78 expression in HepJ5 cells using a small interfering RNA (siRNA), and the proliferation assay and migration assay were performed.

Results: Using siRNA technique, we could successfully reduce GRP78 expression levels in HepJ5 cells. In a cell growth study, we found that GRP78-siRNA caused no significant changes in cellular proliferation in 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT), colony formation, and cell cycle distribution. In a cell migration study, we found that GRP78-siRNA HepJ5 cells had dramatically increased migration ability in Transwell assay.

Conclusions: We conclude that ectopically expressed GRP78 does not contribute to the increased proliferation of HepJ5 cells, but does correlate with the migration of HCC cells under normoxic conditions.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Biomarkers, Tumor / genetics*
  • Carcinoma, Hepatocellular / genetics*
  • Carcinoma, Hepatocellular / metabolism
  • Carcinoma, Hepatocellular / pathology
  • Cell Line, Tumor
  • Cell Movement / genetics*
  • Cell Proliferation
  • Endoplasmic Reticulum Chaperone BiP
  • Gene Silencing*
  • Heat-Shock Proteins / genetics*
  • Humans
  • Liver Neoplasms / genetics*
  • Liver Neoplasms / metabolism
  • Liver Neoplasms / pathology

Substances

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