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http://hdl.handle.net/2445/97701
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DC Field | Value | Language |
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dc.contributor.author | Moreno Càceres, Joaquim | - |
dc.contributor.author | Caja Puigsubirà, Laia | - |
dc.contributor.author | Mainez Villoro, Jessica | - |
dc.contributor.author | Mayoral, R. | - |
dc.contributor.author | Martín Sánz, P. | - |
dc.contributor.author | Moreno Vicente, Roberto | - |
dc.contributor.author | Pozo, Miguel A. del | - |
dc.contributor.author | Dooley, Steven | - |
dc.contributor.author | Egea Guri, Gustavo | - |
dc.contributor.author | Fabregat Romero, Isabel | - |
dc.date.accessioned | 2016-04-20T13:59:39Z | - |
dc.date.available | 2016-04-20T13:59:39Z | - |
dc.date.issued | 2014-07 | - |
dc.identifier.issn | 2041-4889 | - |
dc.identifier.uri | http://hdl.handle.net/2445/97701 | - |
dc.description.abstract | Transforming growth factor-beta (TGF-β) plays a dual role in hepatocytes, inducing both pro- and anti-apoptotic responses, whose balance decides cell fate. Survival signals are mediated by the epidermal growth factor receptor (EGFR) pathway, which is activated by TGF-β in these cells. Caveolin-1 (Cav1) is a structural protein of caveolae linked to TGF-β receptors trafficking and signaling. Previous results have indicated that in hepatocytes, Cav1 is required for TGF-β-induced anti-apoptotic signals, but the molecular mechanism is not fully understood yet. In this work, we show that immortalized Cav1−/− hepatocytes were more sensitive to the pro-apoptotic effects induced by TGF-β, showing a higher activation of caspase-3, higher decrease in cell viability and prolonged increase through time of intracellular reactive oxygen species (ROS). These results were coincident with attenuation of TGF-β-induced survival signals in Cav1−/− hepatocytes, such as AKT and ERK1/2 phosphorylation and NFκ-B activation. Transactivation of the EGFR pathway by TGF-β was impaired in Cav1−/− hepatocytes, which correlated with lack of activation of TACE/ADAM17, the metalloprotease responsible for the shedding of EGFR ligands. Reconstitution of Cav1 in Cav1−/− hepatocytes rescued wild-type phenotype features, both in terms of EGFR transactivation and TACE/ADAM17 activation. TACE/ADAM17 was localized in detergent-resistant membrane (DRM) fractions in Cav1+/+ cells, which was not the case in Cav1−/− cells. Disorganization of lipid rafts after treatment with cholesterol-binding agents caused loss of TACE/ADAM17 activation after TGF-β treatment. In conclusion, in hepatocytes, Cav1 is required for TGF-β-mediated activation of the metalloprotease TACE/ADAM17 that is responsible for shedding of EGFR ligands and activation of the EGFR pathway, which counteracts the TGF-β pro-apoptotic effects. Therefore, Cav1 contributes to the pro-tumorigenic effects of TGF-β in liver cancer cells. | - |
dc.format.extent | 11 p. | - |
dc.format.mimetype | application/pdf | - |
dc.language.iso | eng | - |
dc.publisher | Nature Publishing Group | - |
dc.relation.isformatof | Reproducció del document publicat a: http://dx.doi.org/10.1038/cddis.2014.294 | - |
dc.relation.ispartof | Cell Death and Disease, 2014, vol. 5, p. e1326 | - |
dc.relation.uri | http://dx.doi.org/10.1038/cddis.2014.294 | - |
dc.rights | cc-by-nc-sa (c) Moreno Càceres et al., 2014 | - |
dc.rights.uri | http://creativecommons.org/licenses/by-nc-sa/3.0/es | - |
dc.source | Articles publicats en revistes (Ciències Fisiològiques) | - |
dc.subject.classification | Factor de creixement epidèrmic | - |
dc.subject.classification | Apoptosi | - |
dc.subject.classification | Fosforilació | - |
dc.subject.other | Epidermal growth factor | - |
dc.subject.other | Apoptosis | - |
dc.subject.other | Phosphorylation | - |
dc.title | Caveolin-1 is required for TGF-β-induced transactivation of the EGF receptor pathway in hepatocytes through the activation of the metalloprotease TACE/ADAM17 | - |
dc.type | info:eu-repo/semantics/article | - |
dc.type | info:eu-repo/semantics/publishedVersion | - |
dc.identifier.idgrec | 648204 | - |
dc.date.updated | 2016-04-20T13:59:44Z | - |
dc.relation.projectID | info:eu-repo/grantAgreement/EC/FP7/316549/EU//IT-LIVER | - |
dc.rights.accessRights | info:eu-repo/semantics/openAccess | - |
dc.identifier.pmid | 25032849 | - |
Appears in Collections: | Articles publicats en revistes (Ciències Fisiològiques) Publicacions de projectes de recerca finançats per la UE Articles publicats en revistes (Institut d'lnvestigació Biomèdica de Bellvitge (IDIBELL)) |
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648204.pdf | 1.8 MB | Adobe PDF | View/Open |
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