| Literature DB >> 30581152 |
Panagiotis Karras1, Erica Riveiro-Falkenbach2, Estela Cañón1, Cristina Tejedo1, Tonantzin G Calvo1, Raúl Martínez-Herranz1, Direna Alonso-Curbelo1, Metehan Cifdaloz1, Eva Perez-Guijarro1, Gonzalo Gómez-López3, Pilar Ximenez-Embun4, Javier Muñoz4, Diego Megias5, David Olmeda1, Jorge Moscat6, Pablo L Ortiz-Romero2, Jose L Rodríguez-Peralto7, María S Soengas8.
Abstract
Modulators of mRNA stability are not well understood in melanoma, an aggressive tumor with complex changes in the transcriptome. Here we report the ability of p62/SQSTM1 to extend mRNA half-life of a spectrum of pro-metastatic factors. These include FERMT2 and other transcripts with no previous links to melanoma. Transcriptomic, proteomic, and interactomic analyses, combined with validation in clinical biopsies and mouse models, identified a selected set of RNA-binding proteins (RBPs) recruited by p62, with IGF2BP1 as a key partner. This p62-RBP interaction distinguishes melanoma from other tumors where p62 controls autophagy or oxidative stress. The relevance of these data is emphasized by follow-up analyses of patient prognosis revealing p62 and FERMT2 as adverse determinants of disease-free survival.Entities:
Keywords: FERMT2; IGF2BP1; RNA-binding proteins; gene networks; genetically engineered mouse models; interactomics; melanoma; metastasis; p62/SQSTM1; prognostic indicators; proteomics; transcriptomics
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Year: 2018 PMID: 30581152 DOI: 10.1016/j.ccell.2018.11.008
Source DB: PubMed Journal: Cancer Cell ISSN: 1535-6108 Impact factor: 31.743