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Updated: Sep 24, 2025
10:37
Induction and Analysis of Epithelial to Mesenchymal Transition
Published on: August 27, 2013
36.0K
Exploring YAP1-centered networks linking dysfunctional CFTR to epithelial-mesenchymal transition
Margarida C Quaresma1, Hugo M Botelho1, Ines Pankonien1
1BioISI-Biosystems and Integrative Sciences Institute, Faculty of Sciences, University of Lisboa, Lisboa, Portugal.
Life Science Alliance
|May 2, 2022
Summary
Mutant CFTR causes aberrant YAP1 activity, driving fibrosis and cancer-related epithelial-mesenchymal transition (EMT). Targeting key pathways like Hippo and Wnt may offer new therapies for cystic fibrosis (CF) and cancer.
Area of Science:
- Cell Biology
- Molecular Biology
- Systems Biology
Background:
- Cystic Fibrosis (CF) is caused by CFTR anion channel mutations.
- CFTR mutations are linked to increased cancer incidence.
- The link between CFTR dysfunction and epithelial-mesenchymal transition (EMT) is not fully understood.
Purpose of the Study:
- To elucidate the pathways connecting dysfunctional CFTR to EMT.
- To identify potential therapeutic targets for CF and cancer.
Main Methods:
- Systems biology approach.
- Analysis of YAP1 activity and interactions in cells with wild-type (wt) and mutant CFTR (F508del).
- Identification of signaling pathway crosstalk.
Main Results:
- YAP1 is aberrantly active with F508del-CFTR, not wt-CFTR.
- YAP1 knockdown rescues F508del-CFTR processing and function.
- Five key pathways (Hippo, Wnt, TGFβ, p53, MYC) link mutant CFTR to EMT.
- Hub proteins mediating pathway crosstalk were identified.
Conclusions:
- YAP1 is a key mediator of fibrotic/EMT processes in CF.
- Dysfunctional CFTR activates YAP1, promoting EMT.
- Identified pathways and hub proteins are potential therapeutic targets for CF and cancer.
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