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EWS-FLI1 impairs aryl hydrocarbon receptor activation by blocking tryptophan breakdown via the kynurenine pathway

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dc.contributor.authorMutz, Cornelia N
dc.contributor.authorSchwentner, Raphaela
dc.contributor.authorKauer, Maximilian O
dc.contributor.authorKatschnig, Anna M
dc.contributor.authorKromp, Florian
dc.contributor.authorAryee, Dave N T
dc.contributor.authorErhardt, Sophie
dc.contributor.authorGoiny, Michel
dc.contributor.authorAlonso, Javier
dc.contributor.authorFuchs, Dietmar
dc.contributor.authorKovar, Heinrich
dc.contributor.funderFWF Austrian Science Fund
dc.contributor.funderUnión Europea. Comisión Europea. 7 Programa Marco
dc.contributor.funderAsociación Pablo Ugarte contra el cáncer infantil
dc.contributor.funderAsociación Infantil Oncológica de Madrid. La hucha de Tomás
dc.contributor.funderFundación la Sonrisa de Alex para la investigación y el tratamiento del sarcoma de Ewing
dc.contributor.funderInstituto de Salud Carlos III
dc.contributor.funderRed Temática de Investigación Cooperativa en Cáncer (RTICC) (España)
dc.contributor.funderSwedish Medical Research Council
dc.contributor.funderMiguelañez
dc.date.accessioned2021-07-02T18:13:00Z
dc.date.available2021-07-02T18:13:00Z
dc.date.issued2016
dc.description.abstractEwing sarcoma (ES) is an aggressive pediatric tumor driven by the fusion protein EWS-FLI1. We report that EWS-FLI1 suppresses TDO2-mediated tryptophan (TRP) breakdown in ES cells. Gene expression and metabolite analyses reveal an EWS-FLI1-dependent regulation of TRP metabolism. TRP consumption increased in the absence of EWS-FLI1, resulting in kynurenine and kynurenic acid accumulation, both aryl hydrocarbon receptor (AHR) ligands. Activated AHR binds to the promoter region of target genes. We demonstrate that EWS-FLI1 knockdown results in AHR nuclear translocation and activation. Our data suggest that EWS-FLI1 suppresses autocrine AHR signaling by inhibiting TDO2-catalyzed TRP breakdown.es_ES
dc.description.peerreviewedSíes_ES
dc.description.sponsorshipThe authors thank Dr. Peter Münzel for providing the pT81/3xDRE plasmid. We also thank Dr. Andreas Heitger posthumously for critical discussion and scientific advice. Austrian Science Fund (FWF), ERA‐NET TransCan project PROVABES, project number I 1225‐B19; European Union's FP7 project ASSET (grant agreement No. 259348). J.A. is supported by Asociación Pablo Ugarte and Miguelañez S.A, ASION‐La Hucha de Tomás, Fundación La Sonrisa de Alex and Instituto de Salud Carlos III (PI12/00816 and Spanish Cancer Network RTICC RD12/0036/0027); the Swedish Medical Research Council (2009‐7053; 2013‐2838).es_ES
dc.format.number14es_ES
dc.format.page2063-75es_ES
dc.format.volume590es_ES
dc.identifier.citationFEBS Lett. 2016 Jul;590(14):2063-75.es_ES
dc.identifier.doi10.1002/1873-3468.12243es_ES
dc.identifier.e-issn1873-3468es_ES
dc.identifier.journalFEBS Letterses_ES
dc.identifier.pubmedID27282934es_ES
dc.identifier.urihttp://hdl.handle.net/20.500.12105/13225
dc.language.isoenges_ES
dc.publisherWiley
dc.relation.projectFECYTinfo:eu-repo/grantAgreement/ES/PI12/00816es_ES
dc.relation.projectFISinfo:eu-repo/grantAgreement/ES/RTICCRD12/0036/0027es_ES
dc.relation.projectIDinfo:eu-repo/grantAgreement/EC/FP7/259348es_ES
dc.relation.publisherversionhttps://doi.org/10.1002/1873-3468.12243es_ES
dc.repisalud.centroISCIII::Instituto de Investigación de Enfermedades Raras (IIER)es_ES
dc.repisalud.institucionISCIIIes_ES
dc.rights.accessRightsopen accesses_ES
dc.rights.licenseAtribución 4.0 Internacional*
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/*
dc.subjectEWS-FLI1es_ES
dc.subjectAryl hydrocarbon receptores_ES
dc.subjectTryptophanes_ES
dc.subject.meshAutocrine Communicationes_ES
dc.subject.meshSignal Transductiones_ES
dc.subject.meshCell Linees_ES
dc.subject.meshHumanses_ES
dc.subject.meshKynureninees_ES
dc.subject.meshOncogene Proteins, Fusiones_ES
dc.subject.meshProto-Oncogene Protein c-fli-1es_ES
dc.subject.meshRNA-Binding Protein EWSes_ES
dc.subject.meshReceptors, Aryl Hydrocarbones_ES
dc.subject.meshTryptophanes_ES
dc.subject.meshTryptophan Oxygenasees_ES
dc.titleEWS-FLI1 impairs aryl hydrocarbon receptor activation by blocking tryptophan breakdown via the kynurenine pathwayes_ES
dc.typeresearch articlees_ES
dc.type.hasVersionVoRes_ES
dspace.entity.typePublication
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