Mutz, Cornelia NSchwentner, RaphaelaKauer, Maximilian OKatschnig, Anna MKromp, FlorianAryee, Dave N TErhardt, SophieGoiny, MichelAlonso, JavierFuchs, DietmarKovar, Heinrich2021-07-022021-07-022016FEBS Lett. 2016 Jul;590(14):2063-75.http://hdl.handle.net/20.500.12105/13225Ewing 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.engVoRhttp://creativecommons.org/licenses/by/4.0/EWS-FLI1Aryl hydrocarbon receptorTryptophanAutocrine CommunicationSignal TransductionCell LineHumansKynurenineOncogene Proteins, FusionProto-Oncogene Protein c-fli-1RNA-Binding Protein EWSReceptors, Aryl HydrocarbonTryptophanTryptophan OxygenaseAtribución 4.0 Internacional27282934590142063-7510.1002/1873-3468.122431873-3468FEBS Lettersopen access