CTHRC1 promotes human colorectal cancer cell proliferation and invasiveness by activating Wnt/PCP signaling

Int J Clin Exp Pathol. 2015 Oct 1;8(10):12793-801. eCollection 2015.

Abstract

Collagen triple helix repeats containing 1 (CTHRC1) participates in vascular remodeling, bone formation, and developmental morphogenesis. Recently, CTHRC1 has been found up-regulated in many solid tumors and contributes to tumorigenesis, but its role in the progression of human colorectal cancer (CRC), remains unclear. In this study, CTHRC1 expression in human CRC cell lines was evaluated by quantitative real-time PCR and immunoblot analyses. The role of CTHRC1 in CRC cell proliferation and extracellular matrix invasion in vitro was analyzed by gene over-expression and recombinant protein. Reporter luciferase assay was used to reveal key relevant signaling pathways involved in CRC cells. The results show that CTHRC1 is secreted both by colorectal epithelia cells and stromal fibroblasts. Recombinant CTHRC1 promotes CRC cell migration and invasion dose-dependently. CTHRC1 overexpression promotes CRC cell migration, invasion and proliferation in vitro. Wnt/PCP signaling but not Wnt/catenin signaling was activates by CTHRC1 in CRC cells. Together, CTHRC1 promotes CRC cell proliferation, migration and invasion in vitro, which is possibly mediated by activating Wnt/PCP pathway.

Keywords: CTHRC1; colorectal cancer; extracellular matrix; metastasis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Movement / genetics
  • Cell Proliferation / genetics*
  • Colorectal Neoplasms / genetics*
  • Colorectal Neoplasms / metabolism
  • Colorectal Neoplasms / pathology
  • Extracellular Matrix Proteins / genetics*
  • Extracellular Matrix Proteins / metabolism
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Neoplasm Invasiveness / genetics*
  • Neoplasm Invasiveness / pathology
  • Signal Transduction / genetics*
  • Wnt Proteins / metabolism*
  • beta Catenin / metabolism*

Substances

  • CTHRC1 protein, human
  • Extracellular Matrix Proteins
  • Wnt Proteins
  • beta Catenin