Overexpression of CTHRC1 in Hepatocellular Carcinoma Promotes Tumor Invasion and Predicts Poor Prognosis
Journal
PLoS ONE
Journal Volume
8
Journal Issue
7
Pages
e70324
Date Issued
2013
Author(s)
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. ? 2013 Chen et al.
SDGs
Other Subjects
beta1 integrin; collagen triple helix repeat containing 1 protein; focal adhesion kinase; glycoprotein; messenger RNA; protein Cdc42; Rac1 protein; RhoA guanine nucleotide binding protein; tumor marker; unclassified drug; adult; advanced cancer; article; cancer cell; cancer inhibition; cancer prognosis; cancer staging; cancer surgery; cell adhesion; cell migration; controlled study; CTHRC1 gene; enzyme activation; extracellular matrix; female; gene; gene function; gene overexpression; genetic association; human; human cell; human tissue; liver cell carcinoma; major clinical study; male; metastasis; microarray analysis; predictive value; protein function; protein induction; protein synthesis inhibition; tumor invasion; tumor volume; Adult; Aged; Antigens, CD29; Carcinoma, Hepatocellular; Cell Adhesion; Cell Movement; Extracellular Matrix; Extracellular Matrix Proteins; Female; Gene Expression; Gene Expression Profiling; Gene Expression Regulation, Neoplastic; Humans; Liver Neoplasms; Male; Middle Aged; Neoplasm Grading; Neoplasm Invasiveness; Neoplasm Staging; Odds Ratio; Prognosis; rhoA GTP-Binding Protein
Type
journal article