Publication: PARP-1 regulates metastatic melanoma through modulation of vimentin-induced malignant transformation.
dc.contributor.author | Rodríguez, María Isabel | |
dc.contributor.author | Peralta-Leal, Andreína | |
dc.contributor.author | O'Valle, Francisco | |
dc.contributor.author | Rodriguez-Vargas, José Manuel | |
dc.contributor.author | Gonzalez-Flores, Ariannys | |
dc.contributor.author | Majuelos-Melguizo, Jara | |
dc.contributor.author | López, Laura | |
dc.contributor.author | Serrano, Santiago | |
dc.contributor.author | García de Herreros, Antonio | |
dc.contributor.author | Rodríguez-Manzaneque, Juan Carlos | |
dc.contributor.author | Fernández, Rubén | |
dc.contributor.author | Moral, Raimundo G Del | |
dc.contributor.author | Almodóvar, José Mariano de | |
dc.contributor.author | Oliver, F Javier | |
dc.contributor.authoraffiliation | [Rodríguez,MI;Peralta-Leal,A; Rodriguez-Vargas,JM;Gonzalez-Flores,A; Majuelos-Melguizo,J; López,L; Serrano,S; Oliver,FJ] Instituto de Parasitología y Biomedicina López Neyra, CSIC, Granada, Spain. [Rodríguez,MI; Almodóvar,JM de] IBIMER, Centro de Investigaciones Biomédicas, Universidad de Granada, Granada, Spain. [Rodríguez,MI] Departamento de Bioquímica y Biología Molecular I, Universidad de Granada, Granada, Spain. [O'Valle,F] Departamento de Anatomía Patológica, Universidad de Granada, Granada, Spain. [García de Herreros,A] Institut Municipal d'Investigació Mèdica (IMIM), Universitat Pompeu Fabra, Barcelona, Spain. [Rodríguez-Manzaneque,JC; Fernández,R] Pfizer-University of Granada-Junta de Andalucía Centre for Genomics and Oncological Research (GENYO), Granada, Spain. [Moral,RG del] Unidad de Anatomía Patológica, Complejo Hospitalario y Áreas Sur y Noreste de Granada, Granada, Spain. | es |
dc.contributor.funder | This work was supported by Ministerio de Ciencia e Innovación SAF2006-01094, SAF2009-13281-C02-01, Fundación La Caixa BM06-219-0 and Junta de Andalucía P07-CTS-0239 and CTS-6602 to FJO, Ministerio de Educación y Ciencia SAF2007-64597; CICYT: SAF2009-13281-C02-02; Junta de Andalucía, P06-CTS- 01385 to JMRdA and grants CEIC (P10-CTS5865) and FEDER-ISCIII (PI10/00883) to JCR-M. AGdH has been funded by grants from ‘‘Fundación Científica de la Asociación Española Contra el Cáncer’’, Ministerio de Ciencia y Tecnología SAF2010-16089, and ‘‘Fundación La Marato´ de TV3’’. JCR-M has been funded by Grants CEIC (P1 = -CTS5865) and FEDER-ISCIII (PI10/00883). | |
dc.date.accessioned | 2014-06-23T08:55:53Z | |
dc.date.available | 2014-06-23T08:55:53Z | |
dc.date.issued | 2013-06-13 | |
dc.description | Journal Article; Research Support, Non-U.S. Gov't; | es |
dc.description.abstract | PARP inhibition can induce anti-neoplastic effects when used as monotherapy or in combination with chemo- or radiotherapy in various tumor settings; however, the basis for the anti-metastasic activities resulting from PARP inhibition remains unknown. PARP inhibitors may also act as modulators of tumor angiogenesis. Proteomic analysis of endothelial cells revealed that vimentin, an intermediary filament involved in angiogenesis and a specific hallmark of EndoMT (endothelial to mesenchymal transition) transformation, was down-regulated following loss of PARP-1 function in endothelial cells. VE-cadherin, an endothelial marker of vascular normalization, was up-regulated in HUVEC treated with PARP inhibitors or following PARP-1 silencing; vimentin over-expression was sufficient to drive to an EndoMT phenotype. In melanoma cells, PARP inhibition reduced pro-metastatic markers, including vasculogenic mimicry. We also demonstrated that vimentin expression was sufficient to induce increased mesenchymal/pro-metastasic phenotypic changes in melanoma cells, including ILK/GSK3-β-dependent E-cadherin down-regulation, Snail1 activation and increased cell motility and migration. In a murine model of metastatic melanoma, PARP inhibition counteracted the ability of melanoma cells to metastasize to the lung. These results suggest that inhibition of PARP interferes with key metastasis-promoting processes, leading to suppression of invasion and colonization of distal organs by aggressive metastatic cells. | es |
dc.description.version | Yes | es |
dc.identifier.citation | Rodríguez MI, Peralta-Leal A, O'Valle F, Rodriguez-Vargas JM, Gonzalez-Flores A, Majuelos-Melguizo J, et al. PARP-1 regulates metastatic melanoma through modulation of vimentin-induced malignant transformation. PLoS Genet.. 2013 ; 9(6):e1003531 | es |
dc.identifier.doi | 10.1371/journal.pgen.1003531 | |
dc.identifier.essn | 1553-7404 | |
dc.identifier.issn | 1553-7390 | |
dc.identifier.pmc | PMC3681683 | |
dc.identifier.pmid | 23785295 | |
dc.identifier.uri | http://hdl.handle.net/10668/1640 | |
dc.journal.title | PLoS Genetics | |
dc.language.iso | en | |
dc.organization | AGS Nordeste de Granada | |
dc.relation.publisherversion | http://www.plosgenetics.org/article/info%3Adoi%2F10.1371%2Fjournal.pgen.1003531 | es |
dc.rights.accessRights | open access | |
dc.subject | Antígenos CD | es |
dc.subject | Neoplasias de la Mama | es |
dc.subject | Cadherinas | es |
dc.subject | Línea Celular Tumoral | es |
dc.subject | Transformación Celular Neoplásica | es |
dc.subject | Perros | es |
dc.subject | Células Endoteliales | es |
dc.subject | Transición Epitelial-Mesenquimal | es |
dc.subject | Femenino | es |
dc.subject | Regulación Neoplásica de la Expresión Génica | es |
dc.subject | Células Endoteliales de la Vena Umbilical Humana | es |
dc.subject | Humanos | es |
dc.subject | Células MCF-7 | es |
dc.subject | Ratones | es |
dc.subject | Melanoma Experimental | es |
dc.subject | Invasividad Neoplásica | es |
dc.subject | Metástasis de la Neoplasia | es |
dc.subject | Poli(ADP-Ribosa) Polimerasas | es |
dc.subject | Vimentina | es |
dc.subject.mesh | Medical Subject Headings::Chemicals and Drugs::Biological Factors::Antigens::Antigens, Surface::Antigens, Differentiation::Antigens, CD | es |
dc.subject.mesh | Medical Subject Headings::Diseases::Neoplasms::Neoplasms by Site::Breast Neoplasms | es |
dc.subject.mesh | Medical Subject Headings::Chemicals and Drugs::Biological Factors::Antigens::Antigens, Surface::Cell Adhesion Molecules::Cadherins | es |
dc.subject.mesh | Medical Subject Headings::Anatomy::Cells::Cells, Cultured::Cell Line::Cell Line, Tumor | es |
dc.subject.mesh | Medical Subject Headings::Diseases::Neoplasms::Neoplastic Processes::Cell Transformation, Neoplastic | es |
dc.subject.mesh | Medical Subject Headings::Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Carnivora::Canidae::Dogs | es |
dc.subject.mesh | Medical Subject Headings::Anatomy::Cells::Epithelial Cells::Endothelial Cells | es |
dc.subject.mesh | Medical Subject Headings::Phenomena and Processes::Cell Physiological Phenomena::Cell Physiological Processes::Cell Transdifferentiation::Epithelial-Mesenchymal Transition | es |
dc.subject.mesh | Medical Subject Headings::Check Tags::Female | es |
dc.subject.mesh | Medical Subject Headings::Phenomena and Processes::Genetic Phenomena::Genetic Processes::Gene Expression Regulation::Gene Expression Regulation, Neoplastic | es |
dc.subject.mesh | Medical Subject Headings::Anatomy::Cells::Epithelial Cells::Endothelial Cells::Human Umbilical Vein Endothelial Cells | es |
dc.subject.mesh | Medical Subject Headings::Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Primates::Haplorhini::Catarrhini::Hominidae::Humans | es |
dc.subject.mesh | Medical Subject Headings::Diseases::Neoplasms::Neoplasms, Experimental::Melanoma, Experimental | es |
dc.subject.mesh | Medical Subject Headings::Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Rodentia::Muridae::Murinae::Mice | es |
dc.subject.mesh | Medical Subject Headings::Diseases::Neoplasms::Neoplastic Processes::Neoplasm Invasiveness | es |
dc.subject.mesh | Medical Subject Headings::Diseases::Neoplasms::Neoplastic Processes::Neoplasm Metastasis | es |
dc.subject.mesh | Medical Subject Headings::Chemicals and Drugs::Enzymes and Coenzymes::Enzymes::Transferases::Glycosyltransferases::Pentosyltransferases::ADP Ribose Transferases::Poly(ADP-ribose) Polymerases | es |
dc.subject.mesh | Medical Subject Headings::Chemicals and Drugs::Macromolecular Substances::Polymers::Biopolymers::Intermediate Filament Proteins::Vimentin | es |
dc.subject.mesh | Medical Subject Headings::Organisms::Eukaryota::Animals | es |
dc.subject.mesh | Medical Subject Headings::Anatomy::Cells::Cells, Cultured::Cell Line::Cell Line, Tumor::MCF-7 Cells | es |
dc.title | PARP-1 regulates metastatic melanoma through modulation of vimentin-induced malignant transformation. | es |
dc.type | research article | |
dc.type.hasVersion | VoR | |
dspace.entity.type | Publication |
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