Survivin-mediated cancer cell migration through GRP78 and epithelial-mesenchymal transition (EMT) marker expression in Mahlavu cells

Ann Surg Oncol. 2012 Jan;19(1):336-43. doi: 10.1245/s10434-011-1692-5. Epub 2011 Apr 23.

Abstract

Background: Survivin has multiple functions during the progression of cancer. However, the role of survivin in the progression and metastasis of hepatocellular carcinoma (HCC) remains unknown.

Materials and methods: Survivin expression in HCC cells (Mahlavu and Hep3B) was assessed using reverse transcription real-time PCR and Western blot analyses. In addition, survivin expression in HCC cells was manipulated using small interfering RNA (siRNA) or overexpression and proliferation and transwell migration assays were performed to monitor the effect of manipulated survivin expression on the growth rate and migratory ability of the transfected cells.

Results: Among the HCC cell lines tested, we found high endogenous expression of survivin mRNA and protein in Mahlavu cells. After silencing survivin expression in Mahlavu cells, there was a dramatic decrease in the cell growth rate and an increase in the metastatic potential of the cells. Overexpression of survivin in Hep3B cells suppressed the ability of the cell to migrate. The mechanism of enhanced cell migration caused by decreased survivin expression is mediated through the downregulation of glucose-regulated protein 78 (GRP78) and the upregulation of the epithelial-mesenchymal transition (EMT) marker, vimentin.

Conclusions: Survivin may mediate metastasis in HCC. The knockdown of survivin expression may enhance cancer metastasis through the downregulation of GRP78 and upregulation of vimentin expression.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Apoptosis
  • Blotting, Western
  • Carcinoma, Hepatocellular / genetics
  • Carcinoma, Hepatocellular / metabolism*
  • Carcinoma, Hepatocellular / pathology*
  • Cell Adhesion
  • Cell Movement*
  • Cell Proliferation
  • Endoplasmic Reticulum Chaperone BiP
  • Epithelial-Mesenchymal Transition*
  • Fluorescent Antibody Technique
  • Gene Expression Regulation, Neoplastic
  • Heat-Shock Proteins / antagonists & inhibitors
  • Heat-Shock Proteins / genetics
  • Heat-Shock Proteins / metabolism*
  • Humans
  • Immunoenzyme Techniques
  • Inhibitor of Apoptosis Proteins / antagonists & inhibitors
  • Inhibitor of Apoptosis Proteins / genetics
  • Inhibitor of Apoptosis Proteins / metabolism*
  • Liver Neoplasms / genetics
  • Liver Neoplasms / metabolism*
  • Liver Neoplasms / pathology*
  • RNA, Messenger / genetics
  • RNA, Small Interfering / genetics
  • Real-Time Polymerase Chain Reaction
  • Survivin
  • Tumor Cells, Cultured
  • Vimentin / genetics
  • Vimentin / metabolism

Substances

  • BIRC5 protein, human
  • Endoplasmic Reticulum Chaperone BiP
  • HSPA5 protein, human
  • Heat-Shock Proteins
  • Inhibitor of Apoptosis Proteins
  • RNA, Messenger
  • RNA, Small Interfering
  • Survivin
  • Vimentin