Down-regulation of frizzled-7 expression decreases survival, invasion and metastatic capabilities of colon cancer cells

Br J Cancer. 2009 Oct 20;101(8):1374-81. doi: 10.1038/sj.bjc.6605307. Epub 2009 Sep 22.

Abstract

Background: The canonical Wnt signalling pathway is activated in most sporadic colorectal cancers (CRCs). We previously reported that FZD7 functions as a receptor for the canonical Wnt signalling pathway in colon cancer cells.

Methods and results: In this study, we examined the function of FZD7 in survival, invasion and metastatic capabilities of colon cancer cells. FZD7_siRNA transfection decreased cell viability of HT-29 and HCT-116 colon cancer cells. Expression of c-Jun, phosphorylation of JNK and c-Jun, and activation of RhoA were suppressed after FZD7_siRNA transfection into HCT-116 cells. In vitro invasion activity and Wnt target gene expression were also reduced in HCT-116 cells transfected with FZD7_siRNA. Liver metastasis of stable FZD7_siRNA HCT-116 cell transfectants in scid mice was decreased to 40-50% compared to controls. The mRNA levels of FZD7 in 135 primary CRC tissues were examined by real-time PCR. FZD7 mRNA levels were significantly higher in stage II, III or IV tumours than in non-tumour tissues (P<0.005), and overall survival was shorter in those patients with higher FZD7 expression (P<0.001).

Conclusion: These data suggest that FZD7 may be involved in enhancement of survival, invasion and metastatic capabilities of colon cancer cells through non-canonical Wnt signalling pathways as well as the canonical pathway.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Survival
  • Colorectal Neoplasms / pathology*
  • Frizzled Receptors / antagonists & inhibitors
  • Frizzled Receptors / genetics
  • Frizzled Receptors / physiology*
  • HCT116 Cells
  • HT29 Cells
  • Humans
  • Liver Neoplasms, Experimental / secondary
  • Mice
  • Mice, SCID
  • Neoplasm Invasiveness
  • RNA, Messenger / analysis
  • RNA, Small Interfering / genetics
  • Receptors, G-Protein-Coupled / antagonists & inhibitors
  • Receptors, G-Protein-Coupled / genetics
  • Receptors, G-Protein-Coupled / physiology*

Substances

  • FZD7 protein, human
  • Frizzled Receptors
  • RNA, Messenger
  • RNA, Small Interfering
  • Receptors, G-Protein-Coupled