BIBLIOS

Document type
Journal articles

Document subtype
Full paper

Title
Exploring YAP1-centered networks linking dysfunctional CFTR to epithelial–mesenchymal transition

Participants in the publication
Margarida C Quaresma (Author)
BioISI
Hugo M Botelho (Author)
Dep. Química e Bioquímica
BioISI
Ines Pankonien (Author)
Dep. Química e Bioquímica
BioISI
Cláudia S Rodrigues (Author)
BioISI - Biosystems & Integrative Sciences Institute
Madalena C Pinto (Author)
BioISI
Pau R Costa (Author)
BioISI
Aires Duarte (Author)
BioISI
Margarida D Amaral (Author)
Dep. Química e Bioquímica
BioISI

Summary
Mutations in the CFTR anion channel cause cystic fibrosis (CF) and have also been related to higher cancer incidence. Previously we proposed that this is linked to an emerging role of functional CFTR in protecting against epithelial–mesenchymal transition (EMT). However, the pathways bridging dysfunctional CFTR to EMT remain elusive. Here, we applied systems biology to address this question. Our data show that YAP1 is aberrantly active in the presence of mutant CFTR, interacting with F508del, but not with wt-CFTR, and that YAP1 knockdown rescues F508del-CFTR processing and function. Subsequent analysis of YAP1 interactors and roles in cells expressing either wt- or F508del-CFTR reveal that YAP1 is an important mediator of the fibrotic/EMT processes in CF. Alongside, five main pathways emerge here as key in linking mutant CFTR to EMT, namely, (1) the Hippo pathway; (2) the Wnt pathway; (3) the TGFβ pathway; (4) the p53 pathway; and (5) MYC signaling. Several potential hub proteins which mediate the crosstalk among these pathways were also identified, appearing as potential therapeutic targets for both CF and cancer.


Where published
Life Science Alliance

Publication Identifiers
ISSN - 2575-1077

Publisher
Life Science Alliance, LLC



Document Identifiers
DOI - https://doi.org/10.26508/lsa.202101326
URL - http://dx.doi.org/10.26508/lsa.202101326