PXD020180

PXD020180 is an original dataset announced via ProteomeXchange.

Title	Ral GTPases promote metastasis by controlling biogenesis and organotropism of exosomes
Description	Cancer extracellular vesicles (EVs) mainly exert pro-tumoral functions by changing the phenotypes of stromal cells to the benefit of tumor growth and metastasis. In particular, they shuttle to distant organs and seed pre-metastatic niches facilitating subsequent colonization by circulating tumor cells. The levels of tumor secreted EVs have been correlated to tumor aggressiveness, however, the link between EV secretion mechanisms, their capacity to form pre-metastatic niches and the actual formation of metastasis remains obscure. Here, we show that two GTPases RalA and RalB control, through the phospholipase PLD1, the homeostasis of multi-vesicular bodies and thereby tune the biogenesis and secretion of a subtype of (pro-metastatic) EVs. Mice experiments revealed that RalA and RalB promote lung metastasis of mammary carcinoma cells without affecting their invasive behaviors. Importantly, we show in vivo that EVs from RalA or RalB depleted cells have limited organotropic capacities and, as a consequence, are less efficient in priming lung metastasis. Furthermore, we show that such EVs lack the adhesion molecule MCAM/CD146, which is responsible for EVs organotropism. Finally, we show that RalA and RalB have increased expression in human breast cancer patients with lung metastasis. Altogether, our study identifies Ral GTPases as central molecules linking the mechanisms of EVs secretion, cargo loading to their capacity to disseminate and induce pre-metastatic niches.
HostingRepository	PRIDE
AnnounceDate	2021-09-09
AnnouncementXML	Submission_2021-09-09_03:39:04.382.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Francois Delalande
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: 10090;
ModificationList	acetylated residue; monohydroxylated residue; iodoacetamide derivatized residue
Instrument	Q Exactive

Revision	Datetime	Status	ChangeLog Entry
0	2020-07-03 03:59:37	ID requested
⏵ 1	2021-09-09 03:39:05	announced

Ghoroghi S, Mary B, Larnicol A, Asokan N, Klein A, Osmani N, Busnelli I, Delalande F, Paul N, Halary S, Gros F, Fouillen L, Haeberle AM, Royer C, Spiegelhalter C, Andr, é, -Gr, é, goire G, Mittelheisser V, Detappe A, Murphy K, Timpson P, Carapito R, Blot-Chabaud M, Gavard J, Carapito C, Vitale N, Lefebvre O, Goetz JG, Hyenne V, Ral GTPases promote breast cancer metastasis by controlling biogenesis and organ targeting of exosomes. Elife, 10():(2021) [pubmed]

submitter keyword: Human, extracellular vesicles, Ral, nanoLCMSMS Prostar Maxquant

Sarah CIANFERANI
contact affiliation	BioOrganic Mass Spectrometry laboratory (LSMBO) Institut Plurisciplinaire Hubert Curien University of Strasbourg. France
contact email	sarah.cianferani@unistra.fr
lab head
Francois Delalande
contact affiliation	CNRS
contact email	delaland@unistra.fr
dataset submitter

Dataset FTP location NOTE: Most web browsers have now discontinued native support for FTP access within the browser window. But you can usually install another FTP app (we recommend FileZilla) and configure your browser to launch the external application when you click on this FTP link. Or otherwise, launch an app that supports FTP (like FileZilla) and use this address: ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2021/09/PXD020180

PRIDE project URI

• PRIDE
  1. PXD020180
     1. Label: PRIDE project
     2. Name: Ral GTPases promote metastasis by controlling biogenesis and organotropism of exosomes