Please use this identifier to cite or link to this item:http://hdl.handle.net/20.500.12105/13225
EWS-FLI1 impairs aryl hydrocarbon receptor activation by blocking tryptophan breakdown via the kynurenine pathway.
FEBS Lett . 2016 ;590(14):2063-75.
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.
Autocrine Communication | Signal Transduction | Cell Line | Humans | Kynurenine | Oncogene Proteins, Fusion | Proto-Oncogene Protein c-fli-1 | RNA-Binding Protein EWS | Receptors, Aryl Hydrocarbon | Tryptophan | Tryptophan Oxygenase
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