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oai:repisalud.isciii.es:20.500.12105/132252025-06-17T09:45:35Zcom_20.500.12105_2052com_20.500.12105_2051col_20.500.12105_19616

00925njm 22002777a 4500 dc Mutz, Cornelia N author Schwentner, Raphaela author Kauer, Maximilian O author Katschnig, Anna M author Kromp, Florian author Aryee, Dave N T author Erhardt, Sophie author Goiny, Michel author Alonso, Javier author Fuchs, Dietmar author Kovar, Heinrich author 2016 Ewing 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. FEBS Lett. 2016 Jul;590(14):2063-75. 10.1002/1873-3468.12243 1873-3468 FEBS Letters 27282934 http://hdl.handle.net/20.500.12105/13225 EWS-FLI1 Aryl hydrocarbon receptor Tryptophan EWS-FLI1 impairs aryl hydrocarbon receptor activation by blocking tryptophan breakdown via the kynurenine pathway