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

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 incre...

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Detalhes bibliográficos
Autores: Mutz, Cornelia N, Schwentner, Raphaela, Kauer, Maximilian O, Katschnig, Anna M, Kromp, Florian, Aryee, Dave N T, Erhardt, Sophie, Goiny, Michel, Alonso, Javier, Fuchs, Dietmar, Kovar, Heinrich
Formato: artículo
Fecha de publicación:2016
País:España
Recursos:Instituto de Salud Carlos III (ISCIII)
Repositorio:Repisalud
Idioma:inglés
OAI Identifier:oai:repisalud.isciii.es:20.500.12105/13225
Acesso em linha:http://hdl.handle.net/20.500.12105/13225
Access Level:acceso abierto
Palavra-chave: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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network_acronym_str ES
network_name_str España
repository_id_str
spelling EWS-FLI1 impairs aryl hydrocarbon receptor activation by blocking tryptophan breakdown via the kynurenine pathwayMutz, Cornelia NSchwentner, RaphaelaKauer, Maximilian OKatschnig, Anna MKromp, FlorianAryee, Dave N TErhardt, SophieGoiny, MichelAlonso, JavierFuchs, DietmarKovar, HeinrichAutocrine CommunicationSignal TransductionCell LineHumansKynurenineOncogene Proteins, FusionProto-Oncogene Protein c-fli-1RNA-Binding Protein EWSReceptors, Aryl HydrocarbonTryptophanTryptophan OxygenaseEwing 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.WileyFWF Austrian Science FundUnión Europea. Comisión Europea. 7 Programa MarcoAsociación Pablo Ugarte contra el cáncer infantilAsociación Infantil Oncológica de Madrid. La hucha de TomásFundación la Sonrisa de Alex para la investigación y el tratamiento del sarcoma de EwingInstituto de Salud Carlos IIIRed Temática de Investigación Cooperativa en Cáncer (RTICC) (España)Swedish Medical Research CouncilMiguelañez20212021-07-0220162016-01-0120162016-01-01research articlehttp://purl.org/coar/resource_type/c_2df8fbb1VoRhttp://purl.org/coar/version/c_970fb48d4fbd8a85info:eu-repo/semantics/articleapplication/pdfhttp://hdl.handle.net/20.500.12105/13225reponame:Repisaludinstname:Instituto de Salud Carlos III (ISCIII)InglésengEuropean Commission http://dx.doi.org/10.13039/501100000780 Seventh Framework Programme 259348open accesshttp://purl.org/coar/access_right/c_abf2Atribución 4.0 Internacionalhttp://creativecommons.org/licenses/by/4.0/info:eu-repo/semantics/openAccessoai:repisalud.isciii.es:20.500.12105/132252026-06-12T12:43:37Z
dc.title.none.fl_str_mv EWS-FLI1 impairs aryl hydrocarbon receptor activation by blocking tryptophan breakdown via the kynurenine pathway
title EWS-FLI1 impairs aryl hydrocarbon receptor activation by blocking tryptophan breakdown via the kynurenine pathway
spellingShingle EWS-FLI1 impairs aryl hydrocarbon receptor activation by blocking tryptophan breakdown via the kynurenine pathway
Mutz, Cornelia N
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
title_short EWS-FLI1 impairs aryl hydrocarbon receptor activation by blocking tryptophan breakdown via the kynurenine pathway
title_full EWS-FLI1 impairs aryl hydrocarbon receptor activation by blocking tryptophan breakdown via the kynurenine pathway
title_fullStr EWS-FLI1 impairs aryl hydrocarbon receptor activation by blocking tryptophan breakdown via the kynurenine pathway
title_full_unstemmed EWS-FLI1 impairs aryl hydrocarbon receptor activation by blocking tryptophan breakdown via the kynurenine pathway
title_sort EWS-FLI1 impairs aryl hydrocarbon receptor activation by blocking tryptophan breakdown via the kynurenine pathway
dc.creator.none.fl_str_mv Mutz, Cornelia N
Schwentner, Raphaela
Kauer, Maximilian O
Katschnig, Anna M
Kromp, Florian
Aryee, Dave N T
Erhardt, Sophie
Goiny, Michel
Alonso, Javier
Fuchs, Dietmar
Kovar, Heinrich
author Mutz, Cornelia N
author_facet Mutz, Cornelia N
Schwentner, Raphaela
Kauer, Maximilian O
Katschnig, Anna M
Kromp, Florian
Aryee, Dave N T
Erhardt, Sophie
Goiny, Michel
Alonso, Javier
Fuchs, Dietmar
Kovar, Heinrich
author_role author
author2 Schwentner, Raphaela
Kauer, Maximilian O
Katschnig, Anna M
Kromp, Florian
Aryee, Dave N T
Erhardt, Sophie
Goiny, Michel
Alonso, Javier
Fuchs, Dietmar
Kovar, Heinrich
author2_role author
author
author
author
author
author
author
author
author
author
dc.contributor.none.fl_str_mv FWF Austrian Science Fund
Unión Europea. Comisión Europea. 7 Programa Marco
Asociación Pablo Ugarte contra el cáncer infantil
Asociación Infantil Oncológica de Madrid. La hucha de Tomás
Fundación la Sonrisa de Alex para la investigación y el tratamiento del sarcoma de Ewing
Instituto de Salud Carlos III
Red Temática de Investigación Cooperativa en Cáncer (RTICC) (España)
Swedish Medical Research Council
Miguelañez
dc.subject.none.fl_str_mv 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
topic 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
description 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.
publishDate 2016
dc.date.none.fl_str_mv 2016
2016-01-01
2016
2016-01-01
2021
2021-07-02
dc.type.none.fl_str_mv research article
http://purl.org/coar/resource_type/c_2df8fbb1
VoR
http://purl.org/coar/version/c_970fb48d4fbd8a85
dc.type.openaire.fl_str_mv info:eu-repo/semantics/article
format article
dc.identifier.none.fl_str_mv http://hdl.handle.net/20.500.12105/13225
url http://hdl.handle.net/20.500.12105/13225
dc.language.none.fl_str_mv Inglés
eng
language_invalid_str_mv Inglés
language eng
dc.relation.none.fl_str_mv European Commission http://dx.doi.org/10.13039/501100000780 Seventh Framework Programme 259348
dc.rights.none.fl_str_mv open access
http://purl.org/coar/access_right/c_abf2
Atribución 4.0 Internacional
http://creativecommons.org/licenses/by/4.0/
dc.rights.openaire.fl_str_mv info:eu-repo/semantics/openAccess
rights_invalid_str_mv open access
http://purl.org/coar/access_right/c_abf2
Atribución 4.0 Internacional
http://creativecommons.org/licenses/by/4.0/
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv Wiley
publisher.none.fl_str_mv Wiley
dc.source.none.fl_str_mv reponame:Repisalud
instname:Instituto de Salud Carlos III (ISCIII)
instname_str Instituto de Salud Carlos III (ISCIII)
reponame_str Repisalud
collection Repisalud
repository.name.fl_str_mv
repository.mail.fl_str_mv
_version_ 1869410537680404480
score 15,811543

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