FZD5 prevents epithelial-mesenchymal transition in gastric cancer

Dan Dong1, Lei Na1,2, Kailing Zhou1

  • 1Department of Pathophysiology, College of Basic Medical Science, China Medical University, Shenyang, People's Republic of China.

Abstract

Insights

Frizzled-5 (FZD5) signaling prevents epithelial-mesenchymal transition (EMT) in gastric cancer, unlike other FZD family members. This pathway, involving ELF3, promotes longer survival and acts as a tumor suppressor.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cell Biology

Background:

  • Frizzled (FZD) proteins are WNT ligand receptors.
  • Several FZD members (FZD2, FZD4, FZD7, FZD8, FZD10) promote cancer cell epithelial-mesenchymal transition (EMT).

Purpose of the Study:

  • To investigate the role of Frizzled-5 (FZD5) in gastric cancer and its association with epithelial-mesenchymal transition (EMT).

Main Methods:

  • Utilized CCLE and TCGA databases to analyze FZD5-EMT association.
  • Assessed EMT markers (CDH1, VIM, ZEB1), cell migration, and morphology.
  • Employed Chromatin Immunoprecipitation (ChIP) and Real-time PCR for transcriptional modulation analysis.
  • Performed Kaplan-Meier survival analysis.

Main Results:

  • FZD5 prevents EMT in gastric cancer, maintaining an epithelial phenotype.
  • FZD5 is negatively regulated by SNAI2 and TEAD1; ELF3 is a downstream effector.
  • FZD5 signaling involves LRP5 and WNT7B; ELF3 represses ZEB1.
  • FZD5 and ELF3 correlate with longer survival; SNAI2 and TEAD1 correlate with shorter survival.

Conclusions:

  • FZD5-ELF3 signaling inhibits EMT and acts as a tumor suppressor in gastric cancer.
  • This pathway represents a potential therapeutic target for gastric cancer treatment.

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