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G protein-coupled receptor kinase 2 (GRK2) promotes breast tumorigenesis through a HDAC6-Pin1 Axis
dc.contributor.author | Nogués, Laura | |
dc.contributor.author | Reglero, Clara | |
dc.contributor.author | Rivas, Verónica | |
dc.contributor.author | Salcedo, Alicia | |
dc.contributor.author | Lafarga, Vanesa | |
dc.contributor.author | Neves, María | |
dc.contributor.author | Ramos, Paula | |
dc.contributor.author | Mendiola, Marta | |
dc.contributor.author | Berjón, Alberto | |
dc.contributor.author | Stamatakis Andriani, Konstantinos | |
dc.contributor.author | Zhou, Xiao Zhen | |
dc.contributor.author | Lu, Kun Ping | |
dc.contributor.author | Hardisson Hernáez, David Alonso | |
dc.contributor.author | Mayor Menéndez, Federico | |
dc.contributor.author | Penela Márquez, Petronila | |
dc.contributor.other | UAM. Departamento de Anatomía Patológica | es_ES |
dc.contributor.other | Centro de Biología Molecular Severo Ochoa (CBM) | es_ES |
dc.contributor.other | Instituto de Investigación Sanitaria Hospital Universitario de La Paz (IdiPAZ) | es_ES |
dc.date.accessioned | 2017-04-25T16:53:14Z | |
dc.date.available | 2017-04-25T16:53:14Z | |
dc.date.issued | 2016-11-01 | |
dc.identifier.citation | EBioMedicine 13 (2016): 132–145 | en_US |
dc.identifier.issn | 2352-3964 | es_ES |
dc.identifier.uri | http://hdl.handle.net/10486/678023 | |
dc.description.abstract | In addition to oncogenic drivers, signaling nodes can critically modulate cancer-related cellular networks to strength tumor hallmarks. We identify G-protein-coupled receptor kinase 2 (GRK2) as a relevant player in breast cancer. GRK2 is up-regulated in breast cancer cell lines, in spontaneous tumors in mice, and in a proportion of invasive ductal carcinoma patients. Increased GRK2 functionality promotes the phosphorylation and activation of the Histone Deacetylase 6 (HDAC6) leading to de-acetylation of the Prolyl Isomerase Pin1, a central modulator of tumor progression, thereby enhancing its stability and functional interaction with key mitotic regulators. Interestingly, a correlation between GRK2 expression and Pin1 levels and de-acetylation status is detected in breast cancer patients. Activation of the HDAC6-Pin1 axis underlies the positive effects of GRK2 on promoting growth factor signaling, cellular proliferation and anchorage-independent growth in both luminal and basal breast cancer cells. Enhanced GRK2 levels promote tumor growth in mice, whereas GRK2 down-modulation sensitizes cells to therapeutic drugs and abrogates tumor formation. Our data suggest that GRK2 acts as an important onco-modulator by strengthening the functionality of key players in breast tumorigenesis such as HDAC6 and Pin1. | en_US |
dc.description.sponsorship | Our laboratory is funded by grants from Ministerio de Economía y Competitividad (SAF2011-23800 and SAF2014-55511R), the European Union (H2020-MSCA Programme, Grant agreement 64183-ONCORNET), The Cardiovascular Network of Ministerio Sanidad y Consumo-Instituto Carlos III (RD12/0042/0012), Comunidad de Madrid (S-2010/BMD-2332) to F.M and Instituto Carlos III (PI11/00859, PI14-00435, PIE-13-00041), Fundación Ramón Areces and Fundación Rodríguez Pascual to P.P. Dr.MartaMendiola is supported by a postdoctoral research contract of Fondo de Investigación Sanitaria (FIS) (‘Sara Borrell’ Program), Instituto de Salud Carlos III | en_US |
dc.format.extent | 14 pag. | es_ES |
dc.format.mimetype | application/pdf | en |
dc.language.iso | eng | en |
dc.publisher | Elsevier B.V. | en_US |
dc.relation.ispartof | EBioMedicine | en_US |
dc.rights | © 2016 The Authors | en_US |
dc.subject.other | Acetylation | en_US |
dc.subject.other | Breast transformation | en_US |
dc.subject.other | Cancer | en_US |
dc.subject.other | GRK2 | en_US |
dc.subject.other | HDAC6 | en_US |
dc.subject.other | Pin1 | en_US |
dc.title | G protein-coupled receptor kinase 2 (GRK2) promotes breast tumorigenesis through a HDAC6-Pin1 Axis | en_US |
dc.type | article | en |
dc.subject.eciencia | Medicina | es_ES |
dc.relation.publisherversion | http://dx.doi.org/10.1016/j.ebiom.2016.09.030 | es_ES |
dc.identifier.doi | 10.1016/j.ebiom.2016.09.030 | es_ES |
dc.identifier.publicationfirstpage | 132 | es_ES |
dc.identifier.publicationlastpage | 145 | es_ES |
dc.identifier.publicationvolume | 13 | es_ES |
dc.relation.projectID | Gobierno de España. SAF2011-23800 | es_ES |
dc.relation.projectID | Gobierno de España. SAF2014-55511R | es_ES |
dc.relation.projectID | info:eu-repo/grantAgreement/EC/FP7/64183 | es_ES |
dc.relation.projectID | Comunidad de Madrid. S-2010/BMD-2332/INDISNET | es_ES |
dc.type.version | info:eu-repo/semantics/publishedVersion | en |
dc.rights.cc | Reconocimiento – NoComercial – SinObraDerivada | es_ES |
dc.rights.accessRights | openAccess | en |
dc.authorUAM | Hardisson Hernáez, David Alonso (260363) | |
dc.authorUAM | Lafarga Berciano, Vanesa (264422) | |
dc.authorUAM | Mayor Menendez, Federico (260516) | |
dc.authorUAM | Nogues Vera, Laura (264281) | |
dc.authorUAM | Penela Márquez, Petronila (260945) | |
dc.facultadUAM | Facultad de Medicina | |
dc.institutoUAM | Centro de Biología Molecular Severo Ochoa (CBMSO) | |
dc.institutoUAM | Instituto de Investigación Sanitaria Hospital Universitario de La Paz (IdiPAZ) |