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

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

doi:http://dx.doi.org/10.1016/j.ccell.2016.10.004

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

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

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.