title: UNR/CSDE1 Drives a Post-transcriptional Program to Promote Melanoma Invasion and Metastasis.
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.
authors.affiliation: Gene Regulation, Stem Cells and Cancer Programme, Centre for Genomic Regulation (CRG), The Barcelona Institute of Science and Technology, 08003 Barcelona, Spain; Universitat Pompeu Fabra (UPF), 08003 Barcelona, Spain.
authors.forename: Laurence
authors.initials: L
authors.lastname: Wurth
authors.affiliation: Gene Regulation, Stem Cells and Cancer Programme, Centre for Genomic Regulation (CRG), The Barcelona Institute of Science and Technology, 08003 Barcelona, Spain; Universitat Pompeu Fabra (UPF), 08003 Barcelona, Spain.
authors.forename: Panagiotis
authors.initials: P
authors.lastname: Papasaikas
authors.affiliation: Molecular Oncology Programme, Spanish National Cancer Research Centre (CNIO), 28029 Madrid, Spain.
authors.forename: David
authors.initials: D
authors.lastname: Olmeda
authors.affiliation: Section Molecular Cell Biology, Institute of Molecular Medicine (IMM), Martin-Luther-University (MLU), 06120 Halle, Germany.
authors.forename: Nadine
authors.initials: N
authors.lastname: Bley
authors.affiliation: Molecular Oncology Programme, Spanish National Cancer Research Centre (CNIO), 28029 Madrid, Spain.
authors.forename: Guadalupe T
authors.initials: GT
authors.lastname: Calvo
authors.affiliation: Gene Regulation, Stem Cells and Cancer Programme, Centre for Genomic Regulation (CRG), The Barcelona Institute of Science and Technology, 08003 Barcelona, Spain; Universitat Pompeu Fabra (UPF), 08003 Barcelona, Spain.
authors.forename: Santiago
authors.initials: S
authors.lastname: Guerrero
authors.affiliation: Molecular Oncology Programme, Spanish National Cancer Research Centre (CNIO), 28029 Madrid, Spain.
authors.forename: Daniela
authors.initials: D
authors.lastname: Cerezo-Wallis
authors.affiliation: Translational Oncology Division, Oncohealth Institute - Health Research Institute - University Hospital "Fundacion Jimenez Diaz", 28040 Madrid, Spain.
authors.forename: Javier
authors.initials: J
authors.lastname: Martinez-Useros
authors.affiliation: Molecular Oncology Programme, Spanish National Cancer Research Centre (CNIO), 28029 Madrid, Spain.
authors.forename: María
authors.initials: M
authors.lastname: García-Fernández
authors.affiliation: Section Molecular Cell Biology, Institute of Molecular Medicine (IMM), Martin-Luther-University (MLU), 06120 Halle, Germany.
authors.forename: Stefan
authors.initials: S
authors.lastname: Hüttelmaier
authors.affiliation: Molecular Oncology Programme, Spanish National Cancer Research Centre (CNIO), 28029 Madrid, Spain.
authors.forename: Maria S
authors.initials: MS
authors.lastname: Soengas
authors.affiliation: Gene Regulation, Stem Cells and Cancer Programme, Centre for Genomic Regulation (CRG), The Barcelona Institute of Science and Technology, 08003 Barcelona, Spain; Universitat Pompeu Fabra (UPF), 08003 Barcelona, Spain. Electronic address: fatima.gebauer@crg.eu.
authors.forename: Fátima
authors.initials: F
authors.lastname: Gebauer
mesh_terms: D000818:Animals; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D018450:Disease Progression; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008545:Melanoma / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D051379:Mice; D009361:Neoplasm Invasiveness; D009362:Neoplasm Metastasis; D009368:Neoplasm Transplantation; D012323:RNA Processing, Post-Transcriptional; D016601:RNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D012270:Ribosomes / Q000235:genetics; D017423:Sequence Analysis, RNA / Q000379:methods; D015854:Up-Regulation; D014746:Vimentin / Q000235:genetics*; D020830:rac1 GTP-Binding Protein / Q000235:genetics*
chemical_list: C079950:CSDE1 protein, human; D004268:DNA-Binding Proteins; C107953:RAC1 protein, human; D016601:RNA-Binding Proteins; D014746:Vimentin; D020830:rac1 GTP-Binding Protein
keywords: CSDE1; RAC1; UNR; Vimentin; iCLIP; melanoma; metastasis; ribosome profiling; translation elongation