p62/SQSTM1 Fuels Melanoma Progression by Opposing mRNA Decay of a Selective Set of Pro-metastatic Factors

Cancer Cell. 2019 Jan 14;35(1):46-63.e10. doi: 10.1016/j.ccell.2018.11.008. Epub 2018 Dec 20.


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.

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

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

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


  • FERMT2 protein, human
  • IGF2BP1 protein, human
  • Membrane Proteins
  • Neoplasm Proteins
  • RNA, Messenger
  • RNA-Binding Proteins
  • SQSTM1 protein, human
  • Sequestosome-1 Protein