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dc.contributor.authorMoreno-Vicente, Roberto 
dc.contributor.authorPavon, Dacil Maria 
dc.contributor.authorMartin-Padura, Ines 
dc.contributor.authorCatala-Montoro, Mauro 
dc.contributor.authorDiez-Sanchez, Alberto 
dc.contributor.authorQuilez-Alvarez, Antonio 
dc.contributor.authorLopez, Juan Antonio 
dc.contributor.authorSanchez-Alvarez, Miguel 
dc.contributor.authorVazquez, Jesus 
dc.contributor.authorStrippoli, Raffaele 
dc.contributor.authordel Pozo, Miguel Angel 
dc.date.accessioned2018-11-22T08:10:49Z
dc.date.available2018-11-22T08:10:49Z
dc.date.issued2018
dc.identifierISI:000449476500019
dc.identifier.citationCell Rep. 2018; 25(6):1622-1635
dc.identifier.issn2211-1247
dc.identifier.urihttp://hdl.handle.net/20.500.12105/6660
dc.description.abstractThe transcriptional regulator YAP orchestrates many cellular functions, including tissue homeostasis, organ growth control, and tumorigenesis. Mechanical stimuli are a key input to YAP activity, but the mechanisms controlling this regulation remain largely uncharacterized. We show that CAV1 positively modulates the YAP mechanoresponse to substrate stiffness through actin-cytoskeleton-dependent and Hippo-kinase-independent mechanisms. RHO activity is necessary, but not sufficient, for CAV1-dependent mechanoregulation of YAP activity. Systematic quantitative interactomic studies and image-based small interfering RNA (siRNA) screens provide evidence that this actin-dependent regulation is determined by YAP interaction with the 14-3-3 protein YWHAH. Constitutive YAP activation rescued phenotypes associated with CAV1 loss, including defective extracellular matrix (ECM) remodeling. CAV1-mediated control of YAP activity was validated in vivo in a model of pancreatitis-driven acinar-to-ductal metaplasia. We propose that this CAV1-YAP mechanotransduction system controls a significant share of cell programs linked to these two pivotal regulators, with potentially broad physiological and pathological implications.
dc.description.sponsorshipThis study was supported by the Ministerio de Ciencia, Innovacion y Universidades (grants SAF2011-25047, CSD2009-0016, SAF2014-51876-R, and SAF2017-83130-R and IGP-SO grant MINSEV1512-07-2016), the European Regional Development Fund (ERDF ``A way to make Europe''), Fundacio la Marato de TV3 (grant 674/C/2013), and Worldwide Cancer Research (grant 15-0404) (all to M.A.d.P.). R.M.-V. was supported by Ministerio de Ciencia, Innovacion y Universidades (predoctoral fellowship BES-2012-052980; FPI, SAF2011-25047). We thank the CNIC Microscopy, Genomics, and Bioinformatics Units for technical assistance. Daniel Jimenez-Carretero (Cellomics Unit at CNIC) developed image analysis scripts for the quantitative assessment of actin fiber arrangement. We thank Dr. Paloma Martin-Sanz (IIBM Alberto Sols, Madrid, Spain) for neonatal hepatocytes. Simon Bartlett (CNIC) provided English editing. The CNIC is supported by the Ministerio de Ciencia, Innovacion y Universidades and the Pro CNIC Foundation and is a Severo Ochoa Center of Excellence (SEV-2015-0505).
dc.language.isoeng
dc.publisherCell Press
dc.relation.isversionofPublisher's version
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/*
dc.subjectYES-ASSOCIATED PROTEIN
dc.subjectPANCREATIC DUCTAL ADENOCARCINOMA
dc.subjectHIPPO PATHWAY
dc.subjectLIVER-REGENERATION
dc.subjectPEPTIDE IDENTIFICATION
dc.subjectTUMOR INVASION
dc.subjectGROWTH-CONTROL
dc.subjectSIZE-CONTROL
dc.subjectRHO-GTPASES
dc.subjectSTEM-CELL
dc.titleCaveolin-1 Modulates Mechanotransduction Responses to Substrate Stiffness through Actin-Dependent Control of YAP
dc.typeArtículo
dc.rights.licenseAtribución 4.0 Internacional*
dc.identifier.pubmedID30404014
dc.format.volume25
dc.format.page1622-35
dc.identifier.doi10.1016/j.celrep.2018.10.024
dc.contributor.funderMinisterio de Ciencia, Innovacion y Universidades (España)
dc.contributor.funderEuropean Regional Development Fund (ERDF/FEDER)
dc.contributor.funderFundacio la Marato
dc.contributor.funderWorldwide Cancer Research
dc.contributor.funderFundación ProCNIC
dc.description.peerreviewed
dc.relation.publisherversionhttps://doi.org/10.1016/j.celrep.2018.10.024
dc.identifier.journalCell Reports
dc.repisalud.orgCNICCNIC::Grupos de investigación::Señalización por Integrinas
dc.repisalud.orgCNICCNIC::Grupos de investigación::Proteómica cardiovascular
dc.repisalud.orgCNICCNIC::Unidades técnicas::Proteómica / Metabolómica
dc.repisalud.institucionCNIC
dc.relation.projectIDinfo:eu-repo/grantAgreement/ES/SEV-2015-0505es_ES
dc.relation.projectIDinfo:eu-repo/grantAgreement/ES/SAF2011-25047es_ES
dc.relation.projectIDinfo:eu-repo/grantAgreement/ES/CSD2009-0016es_ES
dc.relation.projectIDinfo:eu-repo/grantAgreement/ES/SAF2014-51876-Res_ES
dc.relation.projectIDinfo:eu-repo/grantAgreement/ES/SAF2017-83130-Res_ES
dc.relation.projectIDinfo:eu-repo/grantAgreement/ES/BES-2012-052980es_ES
dc.relation.projectIDinfo:eu-repo/grantAgreement/ES/MINSEV1512-07-2016es_ES
dc.rights.accessRightsinfo:eu-repo/semantics/openAccesses_ES


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