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

Cancer Res. 2019 Dec 1;79(23):5901-5906. doi: 10.1158/0008-5472.CAN-19-1362. Epub 2019 Aug 20.

Abstract

In the March 1 issue of Cancer Research, 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 Fzd7, 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 adenomatous polyposis coli (Apc) mutation. Apc is located in the cytoplasm downstream of Fzd7 in the Wnt signaling cascade and APC 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.

Publication types

  • Review

MeSH terms

  • Antineoplastic Agents / pharmacology
  • Antineoplastic Agents / therapeutic use
  • Cell Membrane / drug effects
  • Cell Membrane / genetics
  • Cell Membrane / metabolism
  • Frizzled Receptors / antagonists & inhibitors
  • Frizzled Receptors / genetics
  • Frizzled Receptors / metabolism
  • Genetic Heterogeneity*
  • Humans
  • Intracellular Space / drug effects
  • Intracellular Space / genetics
  • Intracellular Space / metabolism
  • Neoplasms / drug therapy
  • Neoplasms / genetics
  • Neoplasms / pathology*
  • Wnt Signaling Pathway / drug effects
  • Wnt Signaling Pathway / genetics*

Substances

  • Antineoplastic Agents
  • Frizzled Receptors