Abstract：
:Unconventional secretion of exosome vesicles from multivesicular endosomes (MVEs) occurs across a broad set of systems and is reported to be upregulated in cancer, where it promotes aggressive behavior. However, regulatory control of exosome secretion is poorly understood. Using cancer cells, we identified specialized invasive actin structures called invadopodia as specific and critical docking and secretion sites for CD63- and Rab27a-positive MVEs. Thus, inhibition of invadopodia formation greatly reduced exosome secretion into conditioned media. Functionally, addition of purified exosomes or inhibition of exosome biogenesis or secretion greatly affected multiple invadopodia life cycle steps, including invadopodia formation, stabilization, and exocytosis of proteinases, indicating a key role for exosome cargoes in promoting invasive activity and providing in situ signaling feedback. Exosome secretion also controlled cellular invasion through three-dimensional matrix. These data identify a synergistic interaction between invadopodia biogenesis and exosome secretion and reveal a fundamental role for exosomes in promoting cancer cell invasiveness.
journal_name
Cell Repjournal_title
Cell reportsauthors
Hoshino D,Kirkbride KC,Costello K,Clark ES,Sinha S,Grega-Larson N,Tyska MJ,Weaver AMdoi
10.1016/j.celrep.2013.10.050subject
Has Abstractpub_date
2013-12-12 00:00:00pages
1159-68issue
5issn
2211-1247pii
S2211-1247(13)00652-9journal_volume
5pub_type
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