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


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).


CONCLUSIONS
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.
Department of Oncology and Laboratory Medicine, Yamaguchi University Graduate School of Medicine, Ube, Yamaguchi, Japan.
K
K
Ueno
S
S
Hazama
S
S
Mitomori
M
M
Nishioka
Y
Y
Suehiro
H
H
Hirata
M
M
Oka
K
K
Imai
R
R
Dahiya
Y
Y
Hinoda
D000818:Animals; D002470:Cell Survival; D015179:Colorectal Neoplasms / Q000473:pathology*; D051157:Frizzled Receptors / Q000037:antagonists & inhibitors / Q000235:genetics / Q000502:physiology*; D045325:HCT116 Cells; D019073:HT29 Cells; D006801:Humans; D008114:Liver Neoplasms, Experimental / Q000556:secondary; D051379:Mice; D016513:Mice, SCID; D009361:Neoplasm Invasiveness; D012333:RNA, Messenger / Q000032:analysis; D034741:RNA, Small Interfering / Q000235:genetics; D043562:Receptors, G-Protein-Coupled / Q000037:antagonists & inhibitors / Q000235:genetics / Q000502:physiology*
C115810:FZD7 protein, human; D051157:Frizzled Receptors; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D043562:Receptors, G-Protein-Coupled