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dc.creatorMarchetto, Arunaes
dc.creatorOhmura, Shunyaes
dc.creatorOrth, Martin F.es
dc.creatorKnott, Maximilian M.L.es
dc.creatorColombo, Maria V.es
dc.creatorRomero Pérez, Lauraes
dc.date.accessioned2023-06-15T13:10:54Z
dc.date.available2023-06-15T13:10:54Z
dc.date.issued2020
dc.identifier.citationMarchetto, A., Ohmura, S., Orth, M.F., Knott, M.M.L., Colombo, M.V. y Romero Pérez, L. (2020). Oncogenic hijacking of a developmental transcription factor evokes vulnerability toward oxidative stress in Ewing sarcoma. Nature Communications, 11 (1), 1-16. https://doi.org/10.1038/s41467-020-16244-2.
dc.identifier.issn2041-1723es
dc.identifier.urihttps://hdl.handle.net/11441/147261
dc.description.abstractEwing sarcoma (EwS) is an aggressive childhood cancer likely originating from mesenchymal stem cells or osteo-chondrogenic progenitors. It is characterized by fusion oncoproteins involving EWSR1 and variable members of the ETS-family of transcription factors (in 85% FLI1). EWSR1-FLI1 can induce target genes by using GGAA-microsatellites as enhancers. Here, we show that EWSR1-FLI1 hijacks the developmental transcription factor SOX6 – a physiological driver of proliferation of osteo-chondrogenic progenitors – by binding to an intronic GGAA-microsatellite, which promotes EwS growth in vitro and in vivo. Through integration of transcriptome-profiling, published drug-screening data, and functional in vitro and in vivo experiments including 3D and PDX models, we discover that constitutively high SOX6 expression promotes elevated levels of oxidative stress that create a therapeutic vulnerability toward the oxidative stress-inducing drug Elesclomol. Collectively, our results exemplify how aberrant activation of a developmental transcription factor by a dominant oncogene can promote malignancy, but provide opportunities for tar- geted therapy.es
dc.formatapplication/pdfes
dc.format.extent16es
dc.language.isoenges
dc.publisherNature Publishing Groupes
dc.relation.ispartofNature Communications, 11 (1), 1-16.
dc.rightsAtribución 4.0 Internacional*
dc.rightsAtribución 4.0 Internacional*
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/*
dc.subjectOncogenic hijackinges
dc.subjectTranscription factores
dc.subjectToward oxidativees
dc.subjectEwing sarcomaes
dc.titleOncogenic hijacking of a developmental transcription factor evokes vulnerability toward oxidative stress in Ewing sarcomaes
dc.typeinfo:eu-repo/semantics/articlees
dcterms.identifierhttps://ror.org/03yxnpp24
dc.type.versioninfo:eu-repo/semantics/publishedVersiones
dc.rights.accessRightsinfo:eu-repo/semantics/openAccesses
dc.contributor.affiliationUniversidad de Sevilla. Departamento de Citología e Histología Normal y Patológicaes
dc.relation.publisherversiontps://doi.org/10.1038/s41467-020-16244-2es
dc.identifier.doi10.1038/s41467-020-16244-2es
dc.journaltitleNature Communicationses
dc.publication.volumen11es
dc.publication.issue1es
dc.publication.initialPage1es
dc.publication.endPage16es

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