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PARP-1 regulates metastatic melanoma through modulation of vimentin-induced malignant transformation.

dc.contributor.authorRodríguez, María Isabel
dc.contributor.authorPeralta-Leal, Andreína
dc.contributor.authorO'Valle, Francisco
dc.contributor.authorRodriguez-Vargas, José Manuel
dc.contributor.authorGonzalez-Flores, Ariannys
dc.contributor.authorMajuelos-Melguizo, Jara
dc.contributor.authorLópez, Laura
dc.contributor.authorSerrano, Santiago
dc.contributor.authorGarcía de Herreros, Antonio
dc.contributor.authorRodríguez-Manzaneque, Juan Carlos
dc.contributor.authorFernández, Rubén
dc.contributor.authorMoral, Raimundo G Del
dc.contributor.authorAlmodóvar, José Mariano de
dc.contributor.authorOliver, 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.funderThis 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.accessioned2014-06-23T08:55:53Z
dc.date.available2014-06-23T08:55:53Z
dc.date.issued2013-06-13
dc.descriptionJournal Article; Research Support, Non-U.S. Gov't;es
dc.description.abstractPARP 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.versionYeses
dc.identifier.citationRodríguez 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):e1003531es
dc.identifier.doi10.1371/journal.pgen.1003531
dc.identifier.essn1553-7404
dc.identifier.issn1553-7390
dc.identifier.pmcPMC3681683
dc.identifier.pmid23785295
dc.identifier.urihttp://hdl.handle.net/10668/1640
dc.journal.titlePLoS Genetics
dc.language.isoen
dc.organizationAGS Nordeste de Granada
dc.relation.publisherversionhttp://www.plosgenetics.org/article/info%3Adoi%2F10.1371%2Fjournal.pgen.1003531es
dc.rights.accessRightsopen access
dc.subjectAntígenos CDes
dc.subjectNeoplasias de la Mamaes
dc.subjectCadherinases
dc.subjectLínea Celular Tumorales
dc.subjectTransformación Celular Neoplásicaes
dc.subjectPerroses
dc.subjectCélulas Endotelialeses
dc.subjectTransición Epitelial-Mesenquimales
dc.subjectFemeninoes
dc.subjectRegulación Neoplásica de la Expresión Génicaes
dc.subjectCélulas Endoteliales de la Vena Umbilical Humanaes
dc.subjectHumanoses
dc.subjectCélulas MCF-7es
dc.subjectRatoneses
dc.subjectMelanoma Experimentales
dc.subjectInvasividad Neoplásicaes
dc.subjectMetástasis de la Neoplasiaes
dc.subjectPoli(ADP-Ribosa) Polimerasases
dc.subjectVimentinaes
dc.subject.meshMedical Subject Headings::Chemicals and Drugs::Biological Factors::Antigens::Antigens, Surface::Antigens, Differentiation::Antigens, CDes
dc.subject.meshMedical Subject Headings::Diseases::Neoplasms::Neoplasms by Site::Breast Neoplasmses
dc.subject.meshMedical Subject Headings::Chemicals and Drugs::Biological Factors::Antigens::Antigens, Surface::Cell Adhesion Molecules::Cadherinses
dc.subject.meshMedical Subject Headings::Anatomy::Cells::Cells, Cultured::Cell Line::Cell Line, Tumores
dc.subject.meshMedical Subject Headings::Diseases::Neoplasms::Neoplastic Processes::Cell Transformation, Neoplastices
dc.subject.meshMedical Subject Headings::Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Carnivora::Canidae::Dogses
dc.subject.meshMedical Subject Headings::Anatomy::Cells::Epithelial Cells::Endothelial Cellses
dc.subject.meshMedical Subject Headings::Phenomena and Processes::Cell Physiological Phenomena::Cell Physiological Processes::Cell Transdifferentiation::Epithelial-Mesenchymal Transitiones
dc.subject.meshMedical Subject Headings::Check Tags::Femalees
dc.subject.meshMedical Subject Headings::Phenomena and Processes::Genetic Phenomena::Genetic Processes::Gene Expression Regulation::Gene Expression Regulation, Neoplastices
dc.subject.meshMedical Subject Headings::Anatomy::Cells::Epithelial Cells::Endothelial Cells::Human Umbilical Vein Endothelial Cellses
dc.subject.meshMedical Subject Headings::Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Primates::Haplorhini::Catarrhini::Hominidae::Humanses
dc.subject.meshMedical Subject Headings::Diseases::Neoplasms::Neoplasms, Experimental::Melanoma, Experimentales
dc.subject.meshMedical Subject Headings::Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Rodentia::Muridae::Murinae::Micees
dc.subject.meshMedical Subject Headings::Diseases::Neoplasms::Neoplastic Processes::Neoplasm Invasivenesses
dc.subject.meshMedical Subject Headings::Diseases::Neoplasms::Neoplastic Processes::Neoplasm Metastasises
dc.subject.meshMedical Subject Headings::Chemicals and Drugs::Enzymes and Coenzymes::Enzymes::Transferases::Glycosyltransferases::Pentosyltransferases::ADP Ribose Transferases::Poly(ADP-ribose) Polymeraseses
dc.subject.meshMedical Subject Headings::Chemicals and Drugs::Macromolecular Substances::Polymers::Biopolymers::Intermediate Filament Proteins::Vimentines
dc.subject.meshMedical Subject Headings::Organisms::Eukaryota::Animalses
dc.subject.meshMedical Subject Headings::Anatomy::Cells::Cells, Cultured::Cell Line::Cell Line, Tumor::MCF-7 Cellses
dc.titlePARP-1 regulates metastatic melanoma through modulation of vimentin-induced malignant transformation.es
dc.typeresearch article
dc.type.hasVersionVoR
dspace.entity.typePublication

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