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 (Po0.005), and overall survival was shorter in those patients with higher FZD7 expression (Po0.001). 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.

WNT5A enhances resistance of melanoma cells to targeted BRAF inhibitors

“…FZD7 has recently garnered attention for its potential connection to the development and progression of multiple cancer subtypes (65). Blocking FZD7 activity with siRNAs or peptides can induce apoptosis and inhibit proliferation in vitro and in vivo in colon, breast, pancreatic, lung, and hepatocellular cancer cells (65)(66)(67)(68)(69). Whether these methods of blocking FZD7 activity could be adapted for the treatment of melanomas or other cancers exhibiting chemotherapeutic resistance due to aberrant hyperactivation of WNT5A-dependent signaling remains to be explored.…”

Anti-Proliferative Effects of Human Anti-FZD7 Single Chain Antibodies on Colorectal Cancer Cells

“…No significant effect on cell growth of SKBR-3 negative cell line was observed for either of these scFv-antibodies. Similarly, knockdown of FZD7 expression by siRNA has resulted in the reduction of colon cancer metastasis (9,39). It has also been reported that inhibition of FZD7 using a dominant negative extracellular domain blocks the growth of human colon cancer cells in vitro and in xenograft animal models (11).…”

Differential Wnt11 Expression Related to Wnt5a in High- and Low-grade Serous Ovarian Cancer: Implications for Migration, Adhesion and Survival

“…Here Wnt11-induced increased cell-matrix adhesion was demonstrated, whether Wnt11 may modulate integrin signaling remains to be determined.Wnt11/Fzd7 was involved in increased invasion of HCT116 colon cancer cells (Ueno et al, 2009). However, here Wnt11 decreased SKOV-3 cell invasion suggesting cell-context dependent functions of Wnt11 on cell invasion.…”

“…A role for Wnt11 in human cancer was first suggested by its high expression in gastric and renal cell carcinoma cell lines, as well as some primary colorectal adenocarcinomas (Kirikoshi et al, 2001). It is highly expressed in some colon cancers (Ueno et al, 2009) and many prostatic tumours express high levels of Wnt11 (Zhu et al, 2004). In contrast, Wnt11 levels are low in hepatocellular carcinomas which plays a tumour suppressor role in this cancer (Toyama et al, 2010).…”