Editors' ChoiceCancer

Autophagy-independent p62 in metastatic melanoma

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Sci. Signal.  05 Feb 2019:
Vol. 12, Issue 567, eaaw8024
DOI: 10.1126/scisignal.aaw8024

By pairing up with RNA-binding proteins, p62 promotes melanoma progression.

In many cancers, autophagy promotes the survival and progression of tumor cells, and the abundance of the autophagy-associated protein p62 is often increased. However, using integrated omics analyses, clinical biopsies, and mouse models, Karras et al. found that, in melanoma cells, p62 promoted metastasis in an autophagy-independent manner. The authors identified a group of RNA-binding proteins with which p62 interacted in melanoma cells. Among these, its interaction with insulin-like growth factor 2 mRNA binding protein 1 (IGF2BP1) increased the stability of the prometastatic mRNA encoding FERMT2, a scaffolding protein that enhances cell adhesion to the extracellular matrix and promotes cell spreading. The abundances of both p62 and FERMT2 were increased in melanoma metastases and correlated with poor prognosis in patients. These findings reveal an unexpected function of p62 and identify potential new targets for therapeutically preventing metastasis in melanoma patients.

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