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

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.

• Authors: K Ueno, S Hazama, S Mitomori, M Nishioka, Y Suehiro, H Hirata, M Oka, K Imai, R Dahiya, Y Hinoda
• Journal: British journal of cancer (Br J Cancer) Vol. 101 Issue 8 Pg. 1374-81 (Oct 20 2009) ISSN: 1532-1827 [Electronic] England
• PMID: 19773752 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

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

Topics

• Animals
• Cell Survival
• Colorectal Neoplasms (pathology)
• Frizzled Receptors (antagonists & inhibitors, genetics, 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, genetics, physiology)