Ral GTPases promote breast cancer metastasis by controlling biogenesis and organ targeting of exosomes

被引：91

作者：

Ghoroghi, Shima ^{[1
,2
,3
]}

Mary, Benjamin ^{[1
,2
,3
]}

Larnicol, Annabel ^{[1
,2
,3
]}

Asokan, Nandini ^{[1
,2
,3
]}

Klein, Annick ^{[1
,2
,3
]}

Osmani, Nael ^{[1
,2
,3
]}

Busnelli, Ignacio ^{[1
,2
,3
]}

Delalande, Francois ^{[4
]}

Paul, Nicodeme ^{[2
,3
,5
]}

Halary, Sebastien ^{[6
]}

Gros, Frederic ^{[1
,2
,3
]}

Fouillen, Laetitia ^{[7
]}

Haeberle, Anne-Marie ^{[8
]}

Royer, Cathy ^{[9
]}

Spiegelhalter, Coralie ^{[10
]}

Andre-Gregoire, Gwennan ^{[11
,12
]}

Mittelheisser, Vincent ^{[1
,2
,3
,13
]}

Detappe, Alexandre ^{[13
,14
]}

Murphy, Kendelle ^{[15
,16
]}

Timpson, Paul ^{[15
,16
]}

Carapito, Raphael ^{[2
,3
,5
]}

Blot-Chabaud, Marcel ^{[17
]}

Gavard, Julie ^{[11
,12
]}

Carapito, Christine ^{[4
]}

Vitale, Nicolas ^{[8
]}

Lefebvre, Olivier ^{[1
,2
,3
]}

Goetz, Jacky G. ^{[1
,2
,3
]}

Hyenne, Vincent ^{[1
,2
,3
,18
]}

机构：

[1] Tumor Biomech, INSERM UMR S1109, Strasbourg, France

[2] Univ Strasbourg, Strasbourg, France

[3] Federat Med Translat Strasbourg FMTS, Strasbourg, France

[4] Univ Strasbourg, Lab Spectrometrie Masse BioOrgan LSMBO, CNRS, IPHC UMR 7178, Strasbourg, France

[5] Genomax, INSERM UMR S1109, Strasbourg, France

[6] Museum Natl Hist Nat Paris, CNRS, UMR MCAM 7245, Paris, France

[7] Univ Bordeaux, Lab Biogenese Membranaire, CNRS, UMR 5200, Villenave Dornon, France

[8] Univ Strasbourg, Ctr Natl Rech Sci, Inst Neurosci Cellulaires & Integrat, Strasbourg, France

[9] Univ Strasbourg, CNRS, Inst Neurosci Cellulaires & Integrat, Strasbourg, France

[10] Univ Strasbourg, IGBMC Imaging Ctr, INSERM, CNRS,UMR7104,U1258, Illkirch Graffenstaden, France

[11] Univ Nantes, Univ Angers, CNRS, Team SOAP,CRCINA,INSERM, Nantes, France

[12] Integrated Ctr Oncol, St Herblain, France

[13] Inst Cancerol Strasbourg Europe, Nanotranslat Lab, Strasbourg, France

[14] Univ Strasbourg, Inst Pluridisciplinaire Hubert Curien IPHC, UMR7178, Equipe Synth Lanal SynPA,CNRS, Strasbourg, France

[15] Univ New South Wales, Fac Med, Vincents Clin Sch, Sydney, NSW, Australia

[16] Garvan Inst Med Res, Kinghorn Canc Ctr, Sydney, NSW, Australia

[17] Aix Marseille Univ, C2VN, Inrae 1260, INSERM 1263, Marseille, France

[18] CNRS SNC5055, Strasbourg, France

来源：

ELIFE | 2021年 / 10卷

基金：

澳大利亚国家健康与医学研究理事会;

关键词：

PHOSPHOLIPASE-D; EXTRACELLULAR VESICLES; THERAPEUTIC TARGETS; PHOSPHATIDIC-ACID; INITIATING CELLS; PROGENITOR CELLS; NICHE FORMATION; CD146; EXPRESSION; PHENOTYPE;

D O I：

10.7554/eLife.61539

中图分类号：

Q [生物科学];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

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, multivesicular 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.

引用

页码：1 / 29

页数：29

共 74 条

[1] HTSeq-a Python']Python framework to work with high-throughput sequencing data [J].

Anders, Simon ;

Pyl, Paul Theodor ;

Huber, Wolfgang .

BIOINFORMATICS, 2015, 31 (02) :166-169

[2] QuPath: Open source software for digital pathology image analysis [J].

Bankhead, Peter ;

Loughrey, Maurice B. ;

Fernandez, Jose A. ;

Dombrowski, Yvonne ;

Mcart, Darragh G. ;

Dunne, Philip D. ;

McQuaid, Stephen ;

Gray, Ronan T. ;

Murray, Liam J. ;

Coleman, Helen G. ;

James, Jacqueline A. ;

Salto-Tellez, Manuel ;

Hamilton, Peter W. .

SCIENTIFIC REPORTS, 2017, 7

[3] Circulating tumour-derived microvesicles in plasma of gastric cancer patients [J].

Baran, Jaroslaw ;

Baj-Krzyworzeka, Monika ;

Weglarczyk, Kazimierz ;

Szatanek, Rafal ;

Zembala, Maria ;

Barbasz, Jakub ;

Czupryna, Antoni ;

Szczepanik, Antoni ;

Zembala, Marek .

CANCER IMMUNOLOGY IMMUNOTHERAPY, 2010, 59 (06) :841-850

[4] CD146 and its Soluble Form Regulate Monocyte Transendothelial Migration [J].

Bardin, Nathalie ;

Blot-Chabaud, Marcel ;

Despoix, Nicolas ;

Kebir, Abdeldjalil ;

Harhouri, Karim ;

Arsanto, Jean-Pierre ;

Espinosa, Leon ;

Perrin, Pierre ;

Robert, Stephane ;

Vely, Frederic ;

Sabatier, Florence ;

Le Bivic, Andre ;

Kaplanski, Gilles ;

Sampol, Jose ;

Dignat-George, Francoise .

ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY, 2009, 29 (05) :746-U286

[5] Extracellular Vesicles in Cancer: Cell-to-Cell Mediators of Metastasis [J].

Becker, Annette ;

Thakur, Basant Kumar ;

Weiss, Joshua Mitchell ;

Kim, Han Sang ;

Peinado, Hector ;

Lyden, David .

CANCER CELL, 2016, 30 (06) :836-848

[6] Proteomic Analysis of Exosomes from Mutant KRAS Colon Cancer Cells Identifies Intercellular Transfer of Mutant KRAS [J].

Beckler, Michelle Demory ;

Higginbotham, James N. ;

Franklin, Jeffrey L. ;

Ham, Amy-Joan ;

Halvey, Patrick J. ;

Imasuen, Imade E. ;

Whitwell, Corbin ;

Li, Ming ;

Liebler, Daniel C. ;

Coffey, Robert J. .

MOLECULAR & CELLULAR PROTEOMICS, 2013, 12 (02) :343-355

[7] Rab27a Supports Exosome-Dependent and -Independent Mechanisms That Modify the Tumor Microenvironment and Can Promote Tumor Progression [J].

Bobrie, Angelique ;

Krumeich, Sophie ;

Reyal, Fabien ;

Recchi, Chiara ;

Moita, Luis F. ;

Seabra, Miguel C. ;

Ostrowski, Matias ;

Thery, Clotilde .

CANCER RESEARCH, 2012, 72 (19) :4920-4930

[8] Phospholipase D Signaling Pathways and Phosphatidic Acid as Therapeutic Targets in Cancer [J].

Bruntz, Ronald C. ;

Lindsley, Craig W. ;

Brown, H. Alex .

PHARMACOLOGICAL REVIEWS, 2014, 66 (04) :1033-1079

[9] KRAS-dependent sorting of miRNA to exosomes [J].

Cha, Diana J. ;

Franklin, Jeffrey L. ;

Dou, Yongchao ;

Liu, Qi ;

Higginbotham, James N. ;

Beckler, Michelle Demory ;

Weaver, Alissa M. ;

Vickers, Kasey ;

Prasad, Nirpesh ;

Levy, Shawn ;

Zhang, Bing ;

Coffey, Robert J. ;

Patton, James G. .

ELIFE, 2015, 4 :22

[10] Transient tissue priming via ROCK inhibition uncouples pancreatic cancer progression, sensitivity to chemotherapy, and metastasis [J].

Chin, Venessa T. ;

Vennin, Claire ;

Warren, Sean C. ;

Lucas, Morghan C. ;

Herrmann, David ;

Magenau, Astrid ;

Melenec, Pauline ;

Walters, Stacey N. ;

Monte-Nieto, Gonzalo dl ;

Conway, James R. W. ;

Nobis, Max ;

Allam, Amr H. ;

McCloy, Rachael A. ;

Currey, Nicola ;

Pinese, Mark ;

Boulghourjian, Alice ;

Zaratzian, Anaiis ;

Adam, Arne A. S. ;

Heu, Celine ;

Nagrial, Adnan M. ;

Chou, Angela ;

Steinmann, Angela ;

Drury, Alison ;

Froio, Danielle ;

Giry-Laterriere, Marc ;

Harris, Nathanial L. E. ;

Phan, Tri ;

Jain, Rohit ;

Weninger, Wolfgang ;

McGhee, Ewan J. ;

Whan, Renee ;

Johns, Amber L. ;

Samra, Jaswinder S. ;

Chantrill, Lorraine ;

Gill, Anthony J. ;

Kohonen-Corish, Maija ;

Harvey, Richard P. ;

Biankin, Andrew V. ;

Evans, T. R. Jeffry ;

Anderson, Kurt I. ;

Grey, Shane T. ;

Ormandy, Christopher J. ;

Gallego-Ortega, David ;

Wang, Yingxiao ;

Samuel, Michael S. ;

Sansom, Owen J. ;

Burgess, Andrew ;

Cox, Thomas R. ;

Morton, Jennifer P. ;

Pajic, Marina .

SCIENCE TRANSLATIONAL MEDICINE, 2017, 9 (384)

← 1 2 3 4 5 6 7 8 →