dc.creator | Marchetto, Aruna | es |
dc.creator | Ohmura, Shunya | es |
dc.creator | Orth, Martin F. | es |
dc.creator | Knott, Maximilian M.L. | es |
dc.creator | Colombo, Maria V. | es |
dc.creator | Romero Pérez, Laura | es |
dc.date.accessioned | 2023-06-15T13:10:54Z | |
dc.date.available | 2023-06-15T13:10:54Z | |
dc.date.issued | 2020 | |
dc.identifier.citation | Marchetto, 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.issn | 2041-1723 | es |
dc.identifier.uri | https://hdl.handle.net/11441/147261 | |
dc.description.abstract | Ewing 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.format | application/pdf | es |
dc.format.extent | 16 | es |
dc.language.iso | eng | es |
dc.publisher | Nature Publishing Group | es |
dc.relation.ispartof | Nature Communications, 11 (1), 1-16. | |
dc.rights | Atribución 4.0 Internacional | * |
dc.rights | Atribución 4.0 Internacional | * |
dc.rights.uri | http://creativecommons.org/licenses/by/4.0/ | * |
dc.subject | Oncogenic hijacking | es |
dc.subject | Transcription factor | es |
dc.subject | Toward oxidative | es |
dc.subject | Ewing sarcoma | es |
dc.title | Oncogenic hijacking of a developmental transcription factor evokes vulnerability toward oxidative stress in Ewing sarcoma | es |
dc.type | info:eu-repo/semantics/article | es |
dcterms.identifier | https://ror.org/03yxnpp24 | |
dc.type.version | info:eu-repo/semantics/publishedVersion | es |
dc.rights.accessRights | info:eu-repo/semantics/openAccess | es |
dc.contributor.affiliation | Universidad de Sevilla. Departamento de Citología e Histología Normal y Patológica | es |
dc.relation.publisherversion | tps://doi.org/10.1038/s41467-020-16244-2 | es |
dc.identifier.doi | 10.1038/s41467-020-16244-2 | es |
dc.journaltitle | Nature Communications | es |
dc.publication.volumen | 11 | es |
dc.publication.issue | 1 | es |
dc.publication.initialPage | 1 | es |
dc.publication.endPage | 16 | es |