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dc.contributor.authorGarcia-Garcia, Laura 
dc.contributor.authorFernández-Tabanera, Enrique
dc.contributor.authorCervera Mayor, Saint Thomas 
dc.contributor.authorMelero-Fernández de Mera, Raquel M 
dc.contributor.authorJosa, Santiago
dc.contributor.authorGonzalez-Gonzalez, Laura 
dc.contributor.authorRodriguez-Martin, Carlos 
dc.contributor.authorGrünewald, Thomas G P
dc.contributor.authorAlonso, Javier
dc.identifier.citationCancers (Basel). 2021 Nov 12;13(22):5668.es_ES
dc.description.abstractEwing sarcoma is a rare pediatric tumor characterized by chromosomal translocations that give rise to aberrant chimeric transcription factors (e.g., EWSR1-FLI1). EWSR1-FLI1 promotes a specific cellular transcriptional program. Therefore, the study of EWSR1-FLI1 target genes is important to identify critical pathways involved in Ewing sarcoma tumorigenesis. In this work, we focused on the transcription factors regulated by EWSR1-FLI1 in Ewing sarcoma. Transcriptomic analysis of the Ewing sarcoma cell line A673 indicated that one of the genes more strongly upregulated by EWSR1-FLI1 was FEZF1 (FEZ family zinc finger protein 1), a transcriptional repressor involved in neural cell identity. The functional characterization of FEZF1 was performed in three Ewing sarcoma cell lines (A673, SK-N-MC, SK-ES-1) through an shRNA-directed silencing approach. FEZF1 knockdown inhibited clonogenicity and cell proliferation. Finally, the analysis of the FEZF1-dependent expression profile in A673 cells showed several neural genes regulated by FEZF1 and concomitantly regulated by EWSR1-FLI1. In summary, FEZF1 is transcriptionally regulated by EWSR1-FLI1 in Ewing sarcoma cells and is involved in the regulation of neural-specific genes, which could explain the neural-like phenotype observed in several Ewing sarcoma tumors and cell lines.es_ES
dc.description.sponsorshipThis research was funded by the Instituto de Salud Carlos III, grant numbers PI20CIII/00020, DTS18CIII/00005, PI16CIII/00026; Asociacion Pablo Ugarte, grant numbers TRPV205/18, TPI-M 1149/13; Asociación Candela Riera, Asociación Todos Somos Iván & Fundación Sonrisa de Alex, grant numbers TVP333-19, TVP-1324/15; ASION, grant number TVP141/17. R.M.M-FdM is supported for a grant of the Spanish Center for Biomedical Network Research on Rare Diseases (CIBERER). The laboratory of T.G.P.G. is supported by the Barbara and Wilfried Mohr Foundation.es_ES
dc.publisherMultidisciplinary Digital Publishing Institute (MDPI) es_ES
dc.subjectEwing sarcomaes_ES
dc.titleThe Transcription Factor FEZF1, a Direct Target of EWSR1-FLI1 in Ewing Sarcoma Cells, Regulates the Expression of Neural-Specific Geneses_ES
dc.typejournal articlees_ES
dc.rights.licenseAtribución 4.0 Internacional*
dc.contributor.funderInstituto de Salud Carlos III es_ES
dc.contributor.funderAsociación Pablo Ugarte contra el cáncer infantil es_ES
dc.contributor.funderCandela Ribera. Asociación contra el sarcoma de Ewing es_ES
dc.contributor.funderAsociación Todos somos Iván es_ES
dc.contributor.funderCentro de Investigación Biomedica en Red - CIBERes_ES
dc.contributor.funderFundación la Sonrisa de Alex para la investigación y el tratamiento del sarcoma de Ewing 
dc.repisalud.centroISCIII::Instituto de Investigación de Enfermedades Rarases_ES
dc.rights.accessRightsopen accesses_ES
dc.relation.projectFISinfo:fis/Instituto de Salud Carlos III/Programa Estatal de Generación de Conocimiento y Fortalecimiento del Sistema Español de I+D+I/Subprograma Estatal de Generación de Conocimiento/PI20-ISCIII Modalidad Proyectos de Investigacion en Salud Intramurales. (2020)/PI20CIII/00020es_ES
dc.relation.projectFISinfo:fis/Instituto de Salud Carlos III/Programa Estatal de Fomento de la Investigación Científica y Técnica de Excelencia/Subprograma Estatal de Generación de Conocimiento/DTS-ISCIII 2018 Modalidad Proyectos de Desarrollo Tecnológico en Salud Intramurales. (2018)/DTS18CIII/00005es_ES
dc.relation.projectFISinfo:fis/Instituto de Salud Carlos III/Programa Estatal de Fomento de la Investigación Científica y Técnica de Excelencia/Subprograma Estatal de Generación de Conocimiento/ISCIII 2016 Modalidad Proyectos de Investigacion en Salud Intramurales. (2016)/PI16CIII/00026es_ES

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