| Title | p62/SQSTM1 Fuels Melanoma Progression by Opposing mRNA Decay of a Selective Set of Pro-metastatic Factors. |
| Publication Type | Journal Article |
| Year of Publication | 2019 |
| Authors | Karras P, Riveiro-Falkenbach E, Cañón E, Tejedo C, Calvo TG, Martínez-Herranz R, Alonso-Curbelo D, Cifdaloz M, Perez-Guijarro E, Gómez-López G, Ximenez-Embun P, Muñoz J, Megias D, Olmeda D, Moscat J, Ortiz-Romero PL, Rodríguez-Peralto JL, Soengas MS |
| Journal | Cancer Cell |
| Volume | 35 |
| Issue | 1 |
| Pagination | 46-63.e10 |
| Date Published | 2019 01 14 |
| ISSN | 1878-3686 |
| Keywords | Animals, Cell Line, Tumor, Disease Progression, Gene Expression Profiling, Gene Expression Regulation, Neoplastic, Humans, Melanoma, Membrane Proteins, Mice, Neoplasm Proteins, Neoplasm Transplantation, Protein Interaction Maps, Proteomics, RNA Stability, RNA, Messenger, RNA-Binding Proteins, Sequestosome-1 Protein, Tissue Array Analysis |
| 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. |
| DOI | 10.1016/j.ccell.2018.11.008 |
| Alternate Journal | Cancer Cell |
| PubMed ID | 30581152 |
Related Faculty:
Jorge Moscat, Ph.D.