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Directed Phenotype Switching as an Effective Antimelanoma Strategy

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dc.contributor.authorSáez Ayala, Magalí
dc.contributor.authorFernández Pérez, María Piedad
dc.contributor.authorChazarra Parres, Soledad
dc.contributor.authorFreter, Rasmus
dc.contributor.authorMiddleton, Mark
dc.contributor.authorPiñero Madrona, Antonio
dc.contributor.authorCabezas Herrera, Juan
dc.contributor.authorGoding, Colin R.
dc.contributor.authorMontenegro Arce, María Fernanda
dc.contributor.authorRodríguez López, José Neptuno
dc.contributor.authorSánchez del Campo Ferrer, Luis
dc.contributor.departmentBioquímica y Biología Molecular Aes
dc.contributor.departmentCirugía, Pediatría y Obstetricia y Ginecologíaes
dc.date.accessioned2024-12-03T07:38:49Z
dc.date.available2024-12-03T07:38:49Z
dc.date.issued2013-06-20
dc.description©2013 Elsevier Inc. This document is the Published Manuscript version of a Published Work that appeared in final form in Cancer cell. To access the final edited and published work see https://doi.org/10.1016/j.ccr.2013.05.009es
dc.description.abstractTherapeutic resistance in melanoma and other cancers arises via irreversible genetic, and dynamic phenotypic, heterogeneity. Here, we use directed phenotype switching in melanoma to sensitize melanoma cells to lineage-specific therapy. We show that methotrexate (MTX) induces microphthalmia-associated transcription factor (MITF) expression to inhibit invasiveness and promote differentiation-associated expression of the melanocyte-specific Tyrosinase gene. Consequently, MTX sensitizes melanomas to a tyrosinase-processed antifolate prodrug 3-O-(3,4,5-trimethoxybenzoyl)-(−)-epicatechin (TMECG), that inhibits the essential enzyme DHFR with high affinity. The combination of MTX and TMECG leads to depletion of thymidine pools, double-strand DNA breaks, and highly efficient E2F1-mediated apoptosis in culture and in vivo. Importantly, this drug combination delivers an effective and tissue-restricted antimelanoma therapy in vitro and in vivo irrespective of BRAF, MEK, or p53 status.es
dc.formatapplication/pdfes
dc.format.extent15es
dc.identifier.citationCancer Cell, volumen 24, número 1, año 2013
dc.identifier.doihttps://doi.org/10.1016/j.ccr.2013.05.009
dc.identifier.issnPrint: 1535-6108
dc.identifier.issnElectronic: 1878-3686
dc.identifier.urihttp://hdl.handle.net/10201/147059
dc.languageenges
dc.publisherCell Presses
dc.relationÁmbito del proyecto: nacional y regional. Agencia financiadora: Ministerio de Ciencia e Innovación y Fundación Séneca, Región de Murcia Código o número del acuerdo de subvención: MICINN; SAF2009-12043-C02-01 y FS-RM; 15230/PI/10es
dc.relation.publisherversionhttps://www.sciencedirect.com/science/article/pii/S1535610813002365es
dc.rights.accessRightsinfo:eu-repo/semantics/restrictedAccess
dc.subjectMelanomaes
dc.subjectCambio fenotípicoes
dc.subjectTerapiaes
dc.subjectMetotrexatoes
dc.subjectDihidrofolatoreductasaes
dc.subject.otherCDU::5 - Ciencias puras y naturales::57 - Biología::577 - Bioquímica. Biología molecular. Biofísicaes
dc.subject.otherCDU::6 - Ciencias aplicadas::61 - Medicina::616 - Patología. Medicina clínica. Oncología::616.5 - Piel. Dermatología clínicaes
dc.titleDirected Phenotype Switching as an Effective Antimelanoma Strategyes
dc.typeinfo:eu-repo/semantics/articlees
dspace.entity.typePublicationes
relation.isAuthorOfPublication2d4e44e6-9dda-4146-8aef-fe0c6b5a8b8f
relation.isAuthorOfPublication36d7ac7e-b9a7-477c-8f7e-f03d4cc834c1
relation.isAuthorOfPublicationf702e5be-3f82-4512-b2a2-6c69a5cb98ff
relation.isAuthorOfPublication.latestForDiscovery2d4e44e6-9dda-4146-8aef-fe0c6b5a8b8f
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