Dysadherin can enhance tumorigenesis by conferring properties of stem-like cells to hepatocellular carcinoma cells

J Hepatol. 2011 Jan;54(1):122-31. doi: 10.1016/j.jhep.2010.06.026. Epub 2010 Aug 26.

Abstract

Background & aims: Hepatocellular carcinoma (HCC) is associated with a high potential for metastasis and disease recurrence, even after surgical resection. The cancer stem cell (CSC) hypothesis proposes that CSCs are responsible for chemo-resistance, recurrence, and metastasis. Dysadherin is a prognostic indicator of metastasis and poor survival in many different cancer types. In this study, we investigated the possible link between dysadherin and CSC in HCC.

Methods: We analyzed the functional implications of dysadherin on cancer stemness by modification of the dysadherin gene in HCC cell lines.

Results: The transfection of dysadherin cDNA into the liver cancer cell line PLC/PRF/5 enhanced the properties of CSCs, including anti-apoptosis, their sphere-forming ability, side population phenotype, and tumor initiation ability in vivo. Furthermore, knockdown of dysadherin in the liver cancer cell line SK-Hep1 suppressed its stem cell-like properties.

Conclusions: These results show that dysadherin give rise to properties of CSC in HCC. Therefore, these findings suggest that dysadherin may be a potential molecular prognostic marker of HCC and may aid in the development of more effective therapies.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • ATP Binding Cassette Transporter, Subfamily B
  • ATP Binding Cassette Transporter, Subfamily B, Member 1 / genetics
  • Animals
  • Apoptosis
  • Biomarkers, Tumor / genetics
  • Biomarkers, Tumor / physiology
  • Carcinoma, Hepatocellular / etiology
  • Carcinoma, Hepatocellular / genetics
  • Carcinoma, Hepatocellular / pathology*
  • Carcinoma, Hepatocellular / physiopathology*
  • Cell Line, Tumor
  • Cell Proliferation
  • Gene Expression Profiling
  • Gene Knockdown Techniques
  • Humans
  • Liver Neoplasms / etiology
  • Liver Neoplasms / genetics
  • Liver Neoplasms / pathology*
  • Liver Neoplasms / physiopathology*
  • Membrane Glycoproteins / antagonists & inhibitors
  • Membrane Glycoproteins / genetics
  • Membrane Glycoproteins / physiology*
  • Mice
  • Mice, Inbred NOD
  • Mice, SCID
  • Neoplasm Proteins / antagonists & inhibitors
  • Neoplasm Proteins / genetics
  • Neoplasm Proteins / physiology*
  • Neoplastic Stem Cells / pathology*
  • Neoplastic Stem Cells / physiology*
  • Prognosis
  • RNA Interference
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • RNA, Neoplasm / genetics
  • RNA, Neoplasm / metabolism
  • Spheroids, Cellular
  • Transfection
  • Tumor Stem Cell Assay

Substances

  • ABCB1 protein, human
  • ATP Binding Cassette Transporter, Subfamily B
  • ATP Binding Cassette Transporter, Subfamily B, Member 1
  • Biomarkers, Tumor
  • FXYD5 protein, human
  • Membrane Glycoproteins
  • Neoplasm Proteins
  • RNA, Messenger
  • RNA, Neoplasm