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Alliance"],"published-print":{"date-parts":[[2022,9]]},"abstract":"<jats:p>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\u2013mesenchymal 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 TGF\u03b2 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.<\/jats:p>","DOI":"10.26508\/lsa.202101326","type":"journal-article","created":{"date-parts":[[2022,5,2]],"date-time":"2022-05-02T15:50:21Z","timestamp":1651506621000},"page":"e202101326","update-policy":"https:\/\/doi.org\/10.26508\/lsa.crossmarkpolicy","source":"Crossref","is-referenced-by-count":11,"title":["Exploring YAP1-centered networks linking dysfunctional CFTR to epithelial\u2013mesenchymal transition"],"prefix":"10.26508","volume":"5","author":[{"given":"Margarida C","family":"Quaresma","sequence":"first","affiliation":[{"name":"BioISI\u2013Biosystems and Integrative Sciences Institute, Faculty of Sciences, University of Lisboa, Lisboa, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4208-1086","authenticated-orcid":true,"given":"Hugo 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