Wnt Signaling in Cancer: Not a Binary ON:OFF Switch

In the March 1 issue of <i>Cancer Research</i>, we identified the Wnt receptor Fzd7 as an attractive therapeutic target for the treatment of gastric cancer. In summary, we showed that pharmacological inhibition of Wnt receptors, or genetic deletion of <i>Fzd7</i>, blocks the initiation and growth of gastric tumors. Inhibiting Fzd receptors, specifically Fzd7, inhibits the growth of gastric cancer cells even in the presence of <i>adenomatous polyposis coli</i> (<i>Apc</i>) mutation. Apc is located in the cytoplasm downstream of Fzd7 in the Wnt signaling cascade and <i>APC</i> mutations activate Wnt/β-catenin signaling, therefore, this result seems counterintuitive. Here, we analyze this result in greater detail in the context of current knowledge of Wnt signaling and discuss the wider implications of this aspect of Wnt signaling in other cancers.