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

• DOI: 10.1016/j.ccell.2016.10.004
• Publication Date: 2016-10-27T16:31:14Z
• Authors: Laurence Wurth; Panagiotis Papasa...; David Olmeda; Nadine Bley; Guadalupe T. Calvo; Santiago Guerrero; Daniela Cerezo-Wa...; Javier Martinez-U...; María García-Fern...; Stefan Hüttelmaier; Maria S. Soengas; Fátima Gebauer
• Keywords: Ribosome profiling

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.