dc.contributor.author | Moreno-Vicente, Roberto | |
dc.contributor.author | Pavon, Dacil Maria | |
dc.contributor.author | Martin-Padura, Ines | |
dc.contributor.author | Catala-Montoro, Mauro | |
dc.contributor.author | Diez-Sanchez, Alberto | |
dc.contributor.author | Quilez-Alvarez, Antonio | |
dc.contributor.author | Lopez, Juan Antonio | |
dc.contributor.author | Sanchez-Alvarez, Miguel | |
dc.contributor.author | Vazquez, Jesus | |
dc.contributor.author | Strippoli, Raffaele | |
dc.contributor.author | del Pozo, Miguel Angel | |
dc.date.accessioned | 2018-11-22T08:10:49Z | |
dc.date.available | 2018-11-22T08:10:49Z | |
dc.date.issued | 2018 | |
dc.identifier | ISI:000449476500019 | |
dc.identifier.citation | Cell Rep. 2018; 25(6):1622-1635 | |
dc.identifier.issn | 2211-1247 | |
dc.identifier.uri | http://hdl.handle.net/20.500.12105/6660 | |
dc.description.abstract | The 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.sponsorship | This 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.iso | eng | |
dc.publisher | Cell Press | |
dc.type.hasVersion | VoR | |
dc.rights.uri | http://creativecommons.org/licenses/by/4.0/ | * |
dc.subject | YES-ASSOCIATED PROTEIN | |
dc.subject | PANCREATIC DUCTAL ADENOCARCINOMA | |
dc.subject | HIPPO PATHWAY | |
dc.subject | LIVER-REGENERATION | |
dc.subject | PEPTIDE IDENTIFICATION | |
dc.subject | TUMOR INVASION | |
dc.subject | GROWTH-CONTROL | |
dc.subject | SIZE-CONTROL | |
dc.subject | RHO-GTPASES | |
dc.subject | STEM-CELL | |
dc.title | Caveolin-1 Modulates Mechanotransduction Responses to Substrate Stiffness through Actin-Dependent Control of YAP | |
dc.type | journal article | |
dc.rights.license | Atribución 4.0 Internacional | * |
dc.identifier.pubmedID | 30404014 | |
dc.format.volume | 25 | |
dc.format.page | 1622-35 | |
dc.identifier.doi | 10.1016/j.celrep.2018.10.024 | |
dc.contributor.funder | Ministerio de Ciencia, Innovación y Universidades (España) | |
dc.contributor.funder | Unión Europea. Fondo Europeo de Desarrollo Regional (FEDER/ERDF) | |
dc.contributor.funder | Fundación La Marató TV3 | |
dc.contributor.funder | Worldwide Cancer Research | |
dc.contributor.funder | Fundación ProCNIC | |
dc.description.peerreviewed | Sí | |
dc.relation.publisherversion | https://doi.org/10.1016/j.celrep.2018.10.024 | |
dc.identifier.journal | Cell Reports | |
dc.repisalud.orgCNIC | CNIC::Grupos de investigación::Señalización por Integrinas | |
dc.repisalud.orgCNIC | CNIC::Grupos de investigación::Proteómica cardiovascular | |
dc.repisalud.orgCNIC | CNIC::Unidades técnicas::Proteómica / Metabolómica | |
dc.repisalud.institucion | CNIC | |
dc.relation.projectID | info:eu-repo/grantAgreement/ES/SEV-2015-0505 | es_ES |
dc.relation.projectID | info:eu-repo/grantAgreement/ES/SAF2011-25047 | es_ES |
dc.relation.projectID | info:eu-repo/grantAgreement/ES/CSD2009-0016 | es_ES |
dc.relation.projectID | info:eu-repo/grantAgreement/ES/SAF2014-51876-R | es_ES |
dc.relation.projectID | info:eu-repo/grantAgreement/ES/SAF2017-83130-R | es_ES |
dc.relation.projectID | info:eu-repo/grantAgreement/ES/BES-2012-052980 | es_ES |
dc.relation.projectID | info:eu-repo/grantAgreement/ES/MINSEV1512-07-2016 | es_ES |
dc.rights.accessRights | open access | es_ES |