UNR/CSDE1 Drives a Post-transcriptional Program to Promote Melanoma Invasion and Metastasis

Publication date: Available online 27 October 2016
Source:Cancer Cell
Author(s): Laurence Wurth, Panagiotis Papasaikas, David Olmeda, Nadine Bley, Guadalupe T. Calvo, Santiago Guerrero, Daniela Cerezo-Wallis, Javier Martinez-Useros, María García-Fernández, Stefan Hüttelmaier, Maria S. Soengas, Fátima Gebauer
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.

Graphical abstract

Teaser

Wurth et al. find that the RNA binding protein UNR is often overexpressed in melanoma and promotes invasion and metastasis. Using iCLIP-seq, RNA-seq, and ribosome profiling, the authors identify potentially oncogenic RNA regulons, one of which includes RAC1 and VIM, whose translation is regulated by UNR.


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