Title:
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UNR/CSDE1 drives a post-transcriptional program to promote melanoma invasion and metastasis
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Author:
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Wurth, Laurence; Papasaikas, Panagiotis; Olmeda, David; Bley, Nadine; Calvo, Guadalupe T.; Guerrero Jijon, Santiago Xavier; Cerezo-Wallis, Daniela; Martínez-Useros, Javier; García-Fernández, María; Hüttelmaier, Stefan; Soengas, María S.; Gebauer, Fátima
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Abstract:
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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. |
Abstract:
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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) |
Subject(s):
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-Melanoma -Metàstasi |
Rights:
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info:eu-repo/semantics/embargoedAccess
© Elsevier http://dx.doi.org/10.1016/j.ccell.2016.10.004 |
Document type:
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Article Article - Accepted version |
Published by:
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Elsevier
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