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)
FACULDADE DE CIÊNCIAS DA UNIVERSIDADE DE LISBOA
BioISI - Biosystems & Integrative Sciences Institute
Hugo M Botelho (Author)
FACULDADE DE CIÊNCIAS DA UNIVERSIDADE DE LISBOA
BioISI - Biosystems & Integrative Sciences Institute
Ines Pankonien (Author)
FACULDADE DE CIÊNCIAS DA UNIVERSIDADE DE LISBOA
BioISI - Biosystems & Integrative Sciences Institute
Cláudia S Rodrigues (Author)
BioISI - Biosystems & Integrative Sciences Institute
FACULDADE DE CIÊNCIAS DA UNIVERSIDADE DE LISBOA
Madalena C Pinto (Author)
FACULDADE DE CIÊNCIAS DA UNIVERSIDADE DE LISBOA
BioISI - Biosystems & Integrative Sciences Institute
Pau R Costa (Author)
FACULDADE DE CIÊNCIAS DA UNIVERSIDADE DE LISBOA
BioISI - Biosystems & Integrative Sciences Institute
Aires Duarte (Author)
FACULDADE DE CIÊNCIAS DA UNIVERSIDADE DE LISBOA
BioISI - Biosystems & Integrative Sciences Institute
Margarida D Amaral (Author)
FACULDADE DE CIÊNCIAS DA UNIVERSIDADE DE LISBOA
BioISI - Biosystems & Integrative Sciences Institute
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.
Date of Publication
2022-05-02
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
Rankings
Web Of Science Q1 (2023) - 3.3 - BIOLOGY
SCIMAGO Q1 (2023) - 1.907 - Biochemistry, Genetics and Molecular Biology (miscellaneous)
SCOPUS Q1 (2023) - 5.8 - Biochemistry, Genetics and Molecular Biology (miscellaneous)
SCIMAGO Q1 (2022) - 1.884 - Biochemistry, Genetics and Molecular Biology (miscellaneous)
Web Of Science Q1 (2022) - 4.4 - BIOLOGY - SCIE
SCOPUS Q1 (2022) - 7 - Biochemistry, Genetics and Molecular Biology (miscellaneous)