关键词: FERMT2 IGF2BP1 RNA-binding proteins gene networks genetically engineered mouse models interactomics melanoma metastasis p62/SQSTM1 prognostic indicators proteomics transcriptomics

Mesh : Animals Cell Line, Tumor Disease Progression Gene Expression Profiling / methods Gene Expression Regulation, Neoplastic Humans Melanoma / genetics metabolism Membrane Proteins / chemistry genetics Mice Neoplasm Proteins / chemistry genetics Neoplasm Transplantation Protein Interaction Maps Proteomics / methods RNA Stability RNA, Messenger / chemistry RNA-Binding Proteins / metabolism Sequestosome-1 Protein / metabolism Tissue Array Analysis

来  源:   DOI:10.1016/j.ccell.2018.11.008   PDF(Sci-hub)

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.
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