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Updated: Nov 16, 2025

Induction and Analysis of Epithelial to Mesenchymal Transition
Published on: August 27, 2013
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.
Background:
Frizzled (FZD) proteins function as receptors for WNT ligands. Members in FZD family including FZD2, FZD4, FZD7, FZD8 and FZD10 have been demonstrated to mediate cancer cell epithelial-mesenchymal transition (EMT).
Methods:
CCLE and TCGA databases were interrogated to reveal the association of FZD5 with EMT. EMT was analyzed by investigating the alterations in CDH1 (E-cadherin), VIM (Vimentin) and ZEB1 expression, cell migration and cell morphology. Transcriptional modulation was determined by ChIP in combination with Real-time PCR. Survival was analyzed by Kaplan-Meier method.
Results:
In contrast to other FZDs, FZD5 was identified to prevent EMT in gastric cancer. FZD5 maintains epithelial-like phenotype and is negatively modulated by transcription factors SNAI2 and TEAD1. Epithelial-specific factor ELF3 is a downstream effecter, and protein kinase C (PKC) links FZD5 to ELF3. ELF3 represses ZEB1 expression, further guarding against EMT. Moreover, FZD5 signaling requires its co-receptor LRP5 and WNT7B is a putative ligand for FZD5. FZD5 and ELF3 are associated with longer survival, whereas SNAI2 and TEAD1 are associated with shorter survival.
Conclusions:
Taken together, FZD5-ELF3 signaling blocks EMT, and plays a potential tumor-suppressing role in gastric cancer. Video 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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