Published:
Proceedings of the National Academy of Sciences, 2017
Published in:
Proceedings of the National Academy of Sciences, 114 (2017) 47, Seite 12495-12500
Language:
English
DOI:
10.1073/pnas.1713433114
ISSN:
1091-6490;
0027-8424
Origination:
Footnote:
Description:
Significance Viral-like nanovesicles of endosomal origin, or “exosomes,” are newly recognized vehicles of signals that cells use to communicate, in various systemic diseases, including cancer. Yet the molecular mechanisms that regulate the biogenesis and activity of exosomes remain obscure. Here, we establish that the oncogenic protein SRC stimulates the secretion of exosomes loaded with syntenin and syndecans, known co-receptors for a plethora of signaling and adhesion molecules. SRC phosphorylates conserved tyrosine residues in the syndecans and syntenin and stimulates their endosomal budding. Moreover, SRC-dependent exosomes have a promigratory activity that strictly depends on syntenin expression. This work sheds light on a function of SRC in cell-to-cell communication and mechanisms of exosome biogenesis and activity, with potential broad impact for physiopathology.