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

Dustin J Flanagan1, Elizabeth Vincan2,3, Toby J Phesse4,5

  • 1Cancer Research UK Beatson Institute, Glasgow, United Kingdom.

Cancer Research
|August 22, 2019
PubMed

Insights

The Wnt receptor Fzd7 is a promising target for gastric cancer therapy. Inhibiting Fzd7 blocks tumor growth, even with mutations in adenomatous polyposis coli (APC).

Area of Science:

  • Oncology
  • Molecular Biology
  • Cancer Research

Background:

  • The Wnt signaling pathway is crucial in cancer development, particularly in gastric cancer.
  • Fzd7 is a Wnt receptor implicated in various cancers.
  • Adenomatous polyposis coli (APC) mutations activate Wnt/β-catenin signaling, a common event in gastric cancer.

Purpose of the Study:

  • To investigate Fzd7 as a therapeutic target for gastric cancer.
  • To analyze the effect of Fzd7 inhibition on gastric tumor initiation and growth.
  • To explore the role of Fzd7 in gastric cancer with APC mutations.

Main Methods:

  • Pharmacological inhibition of Wnt receptors.
  • Genetic deletion of the Fzd7 gene.
  • Analysis of Wnt signaling cascade components.
  • Cell culture and tumor xenograft models.

Main Results:

  • Pharmacological inhibition or genetic deletion of Fzd7 effectively blocked gastric tumor initiation and growth.
  • Fzd7 inhibition suppressed gastric cancer cell growth, irrespective of APC mutation status.
  • This finding appears counterintuitive given APC's role downstream in Wnt signaling.

Conclusions:

  • Fzd7 is a viable therapeutic target for gastric cancer treatment.
  • Targeting Fzd7 offers a potential strategy for overcoming resistance associated with APC mutations.
  • Further investigation into Wnt signaling dynamics in cancer is warranted.

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