| Literature DB >> 33404012 |
Jacky G Goetz1,2,3, Vincent Hyenne1,2,3,4, Shima Ghoroghi1,2,3, Benjamin Mary1,2,3, Annabel Larnicol1,2,3, Nandini Asokan1,2,3, Annick Klein1,2,3, Naël Osmani1,2,3, Ignacio Busnelli1,2,3, François Delalande5, Nicodème Paul2,3,6, Sébastien Halary7, Frédéric Gros1,2,3, Laetitia Fouillen8, Anne-Marie Haeberle9, Cathy Royer10, Coralie Spiegelhalter11, Gwennan André-Grégoire12,13, Vincent Mittelheisser1,2,3,14, Alexandre Detappe14,15, Kendelle Murphy16,17, Paul Timpson16,17, Raphaël Carapito2,3,6, Marcel Blot-Chabaud18, Julie Gavard12,13, Christine Carapito5, Nicolas Vitale9, Olivier Lefebvre1,2,3.
Abstract
Cancer extracellular vesicles (EVs) shuttle at distance and fertilize pre-metastatic niches facilitating subsequent seeding by tumor cells. However, the link between EV secretion mechanisms and their capacity to form pre-metastatic niches remains obscure. Using mouse models, we show that GTPases of the Ral family control, through the phospholipase D1, multi-vesicular bodies homeostasis and tune the biogenesis and secretion of pro-metastatic EVs. Importantly, EVs from RalA or RalB depleted cells have limited organotropic capacities in vivoand are less efficient in promoting metastasis. RalA and RalB reduce the EV levels of the adhesion molecule MCAM/CD146, which favors EV-mediated metastasis by allowing EVs targeting to the lungs. Finally, RalA, RalB, and MCAM/CD146, are factors of poor prognosis in breast cancer patients. Altogether, our study identifies RalGTPases as central molecules linking the mechanisms of EVs secretion and cargo loading to their capacity to disseminate and induce pre-metastatic niches in a CD146-dependent manner.Entities:
Keywords: Ral GTPase; cancer biology; cell biology; exosome; human; mouse; pre-metastatic niche; zebrafish
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Year: 2021 PMID： 33404012 PMCID： PMC7822591 DOI： 10.7554/eLife.61539
Source DB: PubMed Journal: Elife ISSN： 2050-084X Impact factor: 8.140