GHOROGHI, Shima; MARY, Benjamin; LARNICOL, Annabel; ASOKAN, Nandini; KLEIN, Annick; OSMANI, Nael; BUSNELLI, Ignacio; DELALANDE, Francois; PAUL, Nicodeme; HALARY, Sebastien; GROS, Frederic; FOUILLEN, Laetitia; HAEBERLE, Anne Marie; ROYER, Cathy; SPIEGELHALTER, Coralie; ANDRE GREGOIRE, Gwennan; MITTELHEISSER, Vincent; DETAPPE, Alexandre; MURPHY, Kendelle; TIMPSON, Paul; CARAPITO, Raphael; BLOT CHABAUD, Marcel; GAVARD, Julie; CARAPITO, Christine; VITALE, Nicolas; LEFEBVRE, Olivier; GOETZ, Jacky; HYENNE, Vincent

doi:10.7554/eLife.61539

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eLife. 2021, vol. 10, p. 1-29

Resumen en inglés

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 vivo and 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.< Leer menos

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Zebrafish

Mouse

Human

Cell biology

Cancer biology

URI

https://oskar-bordeaux.fr/handle/20.500.12278/136460

DOI

http://dx.doi.org/10.7554/eLife.61539

Proyecto ANR

Infrastructure Française de Protéomique
Etude des fonctions pléiotropiques de l'acide phosphatidique dans la sécrétion régulée à l'aide d'une nouvelle boite à outils moléculaires - ANR-19-CE44-0019
Développement d'une infrastructure française distribuée pour la métabolomique dédiée à l'innovation - ANR-11-INBS-0010

Centros de investigación

Laboratoire de Biogenèse Membranaire (LBM) - UMR 5200