UNR/CSDE1 drives a post-transcriptional program to promote melanoma invasion and metastasis

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• dc.contributor.author Wurth, Laurenceca
• dc.contributor.author Papasaikas, Panagiotisca
• dc.contributor.author Olmeda, Davidca
• dc.contributor.author Bley, Nadineca
• dc.contributor.author Calvo, Guadalupe T.ca
• dc.contributor.author Guerrero Jijon, Santiago Xavierca
• dc.contributor.author Cerezo-Wallis, Danielaca
• dc.contributor.author Martínez-Useros, Javierca
• dc.contributor.author García-Fernández, Maríaca
• dc.contributor.author Hüttelmaier, Stefanca
• dc.contributor.author Soengas, María S.ca
• dc.contributor.author Gebauer, Fátimaca
• dc.date.accessioned 2017-05-26T08:38:17Z
• dc.date.issued 2016
• dc.description.abstract RNA binding proteins (RBPs) modulate cancer progression through poorly understood mechanisms. Here we show that the RBP UNR/CSDE1 is overexpressed in melanoma tumors and promotes invasion and metastasis. iCLIP sequencing, RNA sequencing, and ribosome profiling combined with in silico studies unveiled sets of pro-metastatic factors coordinately regulated by UNR as part of RNA regulons. In addition to RNA steady-state levels, UNR was found to control many of its targets at the level of translation elongation/termination. Key pro-oncogenic targets of UNR included VIM and RAC1, as validated by loss- and gain-of-function studies. Our results identify UNR as an oncogenic modulator of melanoma progression, unravel the underlying molecular mechanisms, and identify potential targets for this therapeutically challenging malignancy.
• dc.description.sponsorship L.W. was supported by the Fonds National de la Recherche, Luxembourg, and cofunded by the Marie Curie Actions of the European Commission (FP7-COFUND) (Project Code 1072489). M.G.-F. was supported by a Juan de la Cierva fellowship from the Spanish Ministry of Economy and Competitiveness (MINECO). This work was supported by MINECO and the European Regional Development Fund (ERDF) under grant BFU2012-37135 and BFU2015-68741 to F.G., and Consolider CSD2009-00080 and TV’13-20131430 (Marató de TV3) grants to F.G. and M.S.S. We acknowledge support of the Spanish Ministry of Economy and Competitiveness, Centro de Excelencia Severo Ochoa 2013–2017, SEV-2012-0208 (to CRG) and SEV-2011-0191 (to CNIO)
• dc.format.mimetype application/pdfca
• dc.identifier.citation Wurth L, Papasaikas P, Olmeda D, Bley N, Calvo GT, Guerrero S et al. UNR/CSDE1 drives a post-transcriptional program to promote melanoma invasion and metastasis. Cancer Cell. 2016 Nov 14;30(5):694-707. DOI: 10.1016/j.ccell.2016.10.004
• dc.identifier.doi http://dx.doi.org/10.1016/j.ccell.2016.10.004
• dc.identifier.issn 1535-6108
• dc.identifier.uri http://hdl.handle.net/10230/32171
• dc.language.iso eng
• dc.publisher Elsevierca
• dc.relation.ispartof Cancer Cell. 2016 Nov 14;30(5):694-707
• dc.relation.projectID info:eu-repo/grantAgreement/EC/FP7/1072489
• dc.relation.projectID info:eu-repo/grantAgreement/ES/3PN/BFU2012-37135
• dc.relation.projectID info:eu-repo/grantAgreement/ES/1PE/BFU2015-68741
• dc.relation.projectID info:eu-repo/grantAgreement/ES/3PN/CSD2009-00080
• dc.rights © Elsevier http://dx.doi.org/10.1016/j.ccell.2016.10.004
• dc.rights.accessRights info:eu-repo/semantics/openAccess
• dc.subject.other Melanoma
• dc.subject.other Metàstasi
• dc.title UNR/CSDE1 drives a post-transcriptional program to promote melanoma invasion and metastasisca
• dc.type info:eu-repo/semantics/article
• dc.type.version info:eu-repo/semantics/acceptedVersion