In conclusion, this study provides valuable insights into the mechanism of the Wnt2-Fzd7 CRD interaction for application in colorectal cancer prevention programs.
Our study reveals a novel RSPO2/Wnt5a-competing noncanonical Wnt signaling mechanism that regulates cellular migration and invasion, and our data suggest that secreted RSPO2 protein could serve as a potential therapy for Wnt5a/Fzd7-driven aggressive CRC tumors.
Recent studies indicated that, among the Fzd family, Fzd7 is the Wnt receptor most commonly upregulated in a variety of cancers including colorectal cancer, hepatocellular carcinoma and triple negative breast cancer.
Our present data demonstrated that FZD7 activates the canonical Wnt pathway in colon cancer cells despite the presence of APC or CTNNB1 mutation and that FZD7-siRNA may be used as a therapeutic reagent for CRCs.
Importantly, we have demonstrated a pivotal role for FZD7 in these phenotype transitions, implicating Wnt signalling in orchestrating CRC morphogenesis.