Overexpression of CTHRC1 in hepatocellular carcinoma promotes tumor invasion and predicts poor prognosis

PLoS One. 2013 Jul 29;8(7):e70324. doi: 10.1371/journal.pone.0070324. Print 2013.

Abstract

Collagen triple helix repeat containing-1 (CTHRC1) is a secreted glycoprotein that activates the planar cell polarity pathway of Wnt signaling. Using microarray analysis, we found that the CTHRC1 gene is overexpressed in hepatocellular carcinoma (HCC). The level of CTHRC1 mRNA was measured in 201 surgically resected HCCs using real time reverse transcription-polymerase chain reaction. Overexpression of CTHRC1 in HCC was associated with large tumor size and advanced tumor stage. Furthermore, expression of CTHRC1 as was identified as an independent prognostic factors in the multivariate analysis. Suppression of CTHRC1 expression inhibited tumor migration and invasion whereas overexpression of CTHRC1 promoted tumor invasion. Activation of RhoA, but not Rac1 or Cdc42, was found to play a crucial role in CTHRC1-induced cell migration. CTHRC1 promoted adhesion of cancer cells to extracellular matrix through induction of integrin β1 expression and activation of focal adhesion kinase. These results suggest CTHRC1 promotes tumor invasion and metastasis by enhancing the adhesion and migratory abilities of tumor cells. It is also a promising biomarker for predicting the prognosis of patients with HCC.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Carcinoma, Hepatocellular / genetics*
  • Carcinoma, Hepatocellular / mortality
  • Carcinoma, Hepatocellular / pathology*
  • Cell Adhesion / genetics
  • Cell Movement / genetics
  • Extracellular Matrix / metabolism
  • Extracellular Matrix Proteins / genetics*
  • Female
  • Gene Expression Profiling
  • Gene Expression Regulation, Neoplastic
  • Gene Expression*
  • Humans
  • Integrin beta1 / genetics
  • Integrin beta1 / metabolism
  • Liver Neoplasms / genetics*
  • Liver Neoplasms / mortality
  • Liver Neoplasms / pathology*
  • Male
  • Middle Aged
  • Neoplasm Grading
  • Neoplasm Invasiveness
  • Neoplasm Staging
  • Odds Ratio
  • Prognosis
  • rhoA GTP-Binding Protein / metabolism

Substances

  • CTHRC1 protein, human
  • Extracellular Matrix Proteins
  • Integrin beta1
  • rhoA GTP-Binding Protein

Grants and funding

This study was supported by a grant from National Science Council, Taiwan, Republic of China. (100-2320-B-002-011-MY3). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.