dc.contributor.author | Palomo Irigoyen, Marta | |
dc.contributor.author | Pérez Andrés, Encarni | |
dc.contributor.author | Iruarrizaga Lejarreta, Marta | |
dc.contributor.author | Barreira Manrique, Adrián | |
dc.contributor.author | Tamayo Caro, Miguel | |
dc.contributor.author | Vila Vecilla, Laura | |
dc.contributor.author | Moreno Cugnon, Leire | |
dc.contributor.author | Beitia, Nagore | |
dc.contributor.author | Medrano, Daniela | |
dc.contributor.author | Fernández Ramos, David | |
dc.contributor.author | Lozano, Juan José | |
dc.contributor.author | Okawa, Satoshi | |
dc.contributor.author | Lavín, José L. | |
dc.contributor.author | Martín Martín, Natalia | |
dc.contributor.author | Sutherland, James D. | |
dc.contributor.author | Guitiérez de Juan, Virginia | |
dc.contributor.author | González López, Monika | |
dc.contributor.author | Macías Cámara, Nuria | |
dc.contributor.author | Mosén Ansorena, David | |
dc.contributor.author | Laraba, Liyam | |
dc.contributor.author | Hanemann, C. Oliver | |
dc.contributor.author | Ercolano, Emanuela | |
dc.contributor.author | Parkinson, David B. | |
dc.contributor.author | Schultz, Christopher W. | |
dc.contributor.author | Araúzo Bravo, Marcos J. | |
dc.contributor.author | Ascensión, Alex M. | |
dc.contributor.author | Gerovska, Daniela | |
dc.contributor.author | Iribar López, Haizea | |
dc.contributor.author | Izeta Permisán, Ander | |
dc.contributor.author | Pytel, Peter | |
dc.contributor.author | Krastel, Philipp | |
dc.contributor.author | Provenzani, Alessandro | |
dc.contributor.author | Seneci, Pierfausto | |
dc.contributor.author | Carrasco, Ruben D. | |
dc.contributor.author | Del Sol, Antonio | |
dc.contributor.author | Martínez Chantar, María Luz | |
dc.contributor.author | Barrio Olano, María Rosa | |
dc.contributor.author | Serra, Eduard | |
dc.contributor.author | Lazaro, Conxi | |
dc.contributor.author | Flanagan, Adrienne M. | |
dc.contributor.author | Gorospe, Myriam | |
dc.contributor.author | Ratner, Nancy | |
dc.contributor.author | Aransay Bañares, Ana María | |
dc.contributor.author | Carracedo Pérez, Arkaitz | |
dc.contributor.author | Varela Rey, Marta | |
dc.contributor.author | Woodhoo, Ashwin | |
dc.date.accessioned | 2021-02-04T08:52:05Z | |
dc.date.available | 2021-02-04T08:52:05Z | |
dc.date.issued | 2020-07-01 | |
dc.identifier.citation | Journal of Clinical Investigation 130(7) : 3848-3864 (2020) | es_ES |
dc.identifier.issn | 0021-9738 | |
dc.identifier.issn | 1558-8238 | |
dc.identifier.uri | http://hdl.handle.net/10810/50014 | |
dc.description.abstract | Cancer cells can develop a strong addiction to discrete molecular regulators, which control the aberrant gene expression programs that drive and maintain the cancer phenotype. Here, we report the identification of the RNA-binding protein HuR/ELAVL1 as a central oncogenic driver for malignant peripheral nerve sheath tumors (MPNSTs), which are highly aggressive sarcomas that originate from cells of the Schwann cell lineage. HuR was found to be highly elevated and bound to a multitude of cancer-associated transcripts in human MPNST samples. Accordingly, genetic and pharmacological inhibition of HuR had potent cytostatic and cytotoxic effects on tumor growth, and strongly suppressed metastatic capacity in vivo. Importantly, we linked the profound tumorigenic function of HuR to its ability to simultaneously regulate multiple essential oncogenic pathways in MPNST cells, including the Wnt/beta-catenin, YAP/TAZ, RB/E2F, and BET pathways, which converge on key transcriptional networks. Given the exceptional dependency of MPNST cells on HuR for survival, proliferation, and dissemination, we propose that HuR represents a promising therapeutic target for MPNST treatment. | es_ES |
dc.description.sponsorship | This work was funded by grants to AW from the Spanish Association Against Cancer (AECC; JP Vizcaya); Spanish Ministry of Science, Innovation and Universities (MCIU)/Agencia Estatal de Investigacion (AEI)/European Regional Development Fund (FEDER), European Union (EU) (Subprograma Ramon y Cajal RYC2010-06901; Proyectos Retos Investigacion RTI2018-097503-B-I00, SAF2015-65360-R; Proyectos Explora Ciencia SAF2015-72416-EXP; Proyectos Europa Excelencia SAF2015-62588-ERC); the BBVA Foundation; Basque Department of Industry, Tourism and Trade (Elkartek) and Education (PI2013-46); Fundacion Vasca de Innovacion e Investigacion Sanitarias EiTB Maratoia (BIO13/CI/015); the Neurofibromatosis Therapeutic Acceleration Program; and the European Research Council (consolidator grant under the EU's Horizon 2020 research and innovation programme; grant agreement 865157). MVR is grateful for the support of a 2017 Leonardo Grant for Researchers and Cultural Creators (BBVA Foundation), Accion Estrategica Ciber Emergentes 2018 (Ciberehd-ISCIII), and Gilead Sciences International Research Scholars Program in Liver Disease. The work of AC is supported by the Basque Department of Industry, Tourism and Trade (Elkartek) and Education (IKERTALDE IT1106-16); the BBVA Foundation; the MCIU/AEI (SAF2016-79381-R [FEDER/EU]; Severo Ochoa Excellence Accreditation SEV-2016-0644; Excellence Networks SAF20168-1975-REDT); the European Training Networks Project (H2020-MSCA-ITN-308 2016 721532); the AECC (IDEAS175CARR, GCTRA18006CARR); La Caixa Foundation (HR17-00094); and the European Research Council (Starting Grant 336343, PoC 754627). MG was supported by the Intramural Research Program of the National Institute on Aging, NIH. MPI is grateful for the support of the Basque Government of Education fellowship. MTC is grateful for the support of "Ayudas para contratos predoctorales para la formacion de doctores" (MCIU/AEI/FEDER, EU). COH acknowledges funding from Brain Tumour Research. RB acknowledges MCIU/AEI/FEDER, EU (BFU2014-52282-P and BFU2017-84653-P). ES and CL are supported by the Carlos III National Health Institute funded by FEDER funds - a way to build Europe (CIBERONC) and the Government of Catalonia (2017SGR496). MLM-C acknowledges support from MCIU/AEI/FEDER, EU (SAF2017-87301-R); Asociacion Espanola Contra El Cancer (AECC); AECC Canceres Raros; BBVA Biomedicina (UMBRELLA); and La CAIXA Foundation (LCF/PR/HP17/52190004). AP was supported by Associazione Italiana Ricerca sul Cancro (AIRC; IG 2018 Id.21548). CIBERehd is funded by the Instituto de Salud Carlos III. We thank MCIU for the Severo Ochoa Excellence Accreditation (SEV-2016-0644). | es_ES |
dc.language.iso | eng | es_ES |
dc.publisher | The American Society for Clinical Investigation | es_ES |
dc.relation | info:eu-repo/grantAgreement/MCIU/RYC2010-06901 | es_ES |
dc.relation | info:eu-repo/grantAgreement/MCIU/RTI2018-097503-B-I00 | es_ES |
dc.relation | info:eu-repo/grantAgreement/MCIU/SAF2015-65360-R | es_ES |
dc.relation | info:eu-repo/grantAgreement/MCIU/SAF2015-72416-EXP | es_ES |
dc.relation | info:eu-repo/grantAgreement/MCIU/SAF2015-62588-ERC | es_ES |
dc.relation | info:eu-repo/grantAgreement/MCIU/SAF2016-79381-R | es_ES |
dc.relation | info:eu-repo/grantAgreement/MCIU/SEV-2016-0644 | es_ES |
dc.relation | info:eu-repo/grantAgreement/MCIU/SAF20168-1975-REDT0 | es_ES |
dc.relation | info:eu-repo/grantAgreement/MCIU/SEV-2016-0644 | es_ES |
dc.relation | info:eu-repo/grantAgreement/MCIU/BFU2017-84653-P | es_ES |
dc.relation | info:eu-repo/grantAgreement/MCIU/SAF2017-87301-R | es_ES |
dc.relation | info:eu-repo/grantAgreement/MCIU/BFU2014-52282-P | es_ES |
dc.relation | info:eu-repo/grantAgreement/EC/H2020/865157 | es_ES |
dc.relation | info:eu-repo/grantAgreement/EC/H2020/721532 | es_ES |
dc.relation | info:eu-repo/grantAgreement/EC/FP7/336343 | es_ES |
dc.relation | info:eu-repo/grantAgreement/EC/H2020/754627 | es_ES |
dc.rights | info:eu-repo/semantics/openAccess | es_ES |
dc.rights.uri | http://creativecommons.org/licenses/by/3.0/es/ | * |
dc.subject | RNA-binding proteins | es_ES |
dc.subject | aurora kinase | es_ES |
dc.subject | enrichment analysis | es_ES |
dc.subject | schwann-cells | es_ES |
dc.subject | RIP-chip | es_ES |
dc.subject | cancer | es_ES |
dc.subject | target | es_ES |
dc.subject | identification | es_ES |
dc.subject | transcription | es_ES |
dc.subject | inhibition | es_ES |
dc.title | HuR/ELAVL1 drives malignant peripheral nerve sheath tumor growth and metastasis | es_ES |
dc.type | info:eu-repo/semantics/article | es_ES |
dc.rights.holder | 2020, Palomo-Irigoyen et al. This is an open access article published under the terms of the Creative Commons Attribution 4.0 International License. | es_ES |
dc.rights.holder | Atribución 3.0 España | * |
dc.relation.publisherversion | https://www.jci.org/articles/view/130379/pdf | es_ES |
dc.identifier.doi | 10.1172/JCI130379 | |
dc.contributor.funder | European Commission | |
dc.departamentoes | Bioquímica y biología molecular | es_ES |
dc.departamentoeu | Biokimika eta biologia molekularra | es_ES |