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

L Wurth, P Papasaikas, D Olmeda, N Bley, GT Calvo… - Cancer cell, 2016 - cell.com
Cancer cell, 2016cell.com
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 …
Summary
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.
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