title: Sortilin mediates the release and transfer of exosomes in concert with two tyrosine kinase receptors.
abstract: The transfer of exosomes containing both genetic and protein materials is necessary for the control of the cancer cell microenvironment to promote tumor angiogenesis. The nature and function of proteins found in the exosomal cargo, and the mechanism of their action in membrane transport and related signaling events are not clearly understood. In this study, we demonstrate, in human lung cancer A549 cells, that the exosome release mechanism is closely linked to the multifaceted receptor sortilin (also called neurotensin receptor 3). Sortilin is already known to be important for cancer cell function. Here, we report for the first time its role in the assembly of a tyrosine kinase complex and subsequent exosome release. This new complex (termed the TES complex) is found in exosomes and results in the linkage of the two tyrosine kinase receptors TrkB (also known as NTRK2) and EGFR with sortilin. Using in vitro models, we demonstrate that this sortilin-containing complex exhibits a control on endothelial cells and angiogenesis activation through exosome transfer.
authors.affiliation: EA3842 Homéostasie Cellulaire et Pathologies and Chaire de Pneumologie Expérimentale, Université de Limoges, Faculté de Médecine, 2 Rue du Dr Raymond Marcland, 87025 Limoges CEDEX-France cornelia.wilson@unilim.fr.
authors.forename: Cornelia M
authors.initials: CM
authors.lastname: Wilson
authors.affiliation: EA3842 Homéostasie Cellulaire et Pathologies and Chaire de Pneumologie Expérimentale, Université de Limoges, Faculté de Médecine, 2 Rue du Dr Raymond Marcland, 87025 Limoges CEDEX-France.
authors.forename: Thomas
authors.initials: T
authors.lastname: Naves
authors.affiliation: EA3842 Homéostasie Cellulaire et Pathologies and Chaire de Pneumologie Expérimentale, Université de Limoges, Faculté de Médecine, 2 Rue du Dr Raymond Marcland, 87025 Limoges CEDEX-France Service de Pathologie Respiratoire, Centre Hospitalier et Universitaire de Limoges, 87000 Limoges CEDEX-France.
authors.forename: François
authors.initials: F
authors.lastname: Vincent
authors.affiliation: Service de Pathologie Respiratoire, Centre Hospitalier et Universitaire de Limoges, 87000 Limoges CEDEX-France.
authors.forename: Boris
authors.initials: B
authors.lastname: Melloni
authors.affiliation: Service de Pathologie Respiratoire, Centre Hospitalier et Universitaire de Limoges, 87000 Limoges CEDEX-France.
authors.forename: François
authors.initials: F
authors.lastname: Bonnaud
authors.affiliation: EA3842 Homéostasie Cellulaire et Pathologies and Chaire de Pneumologie Expérimentale, Université de Limoges, Faculté de Médecine, 2 Rue du Dr Raymond Marcland, 87025 Limoges CEDEX-France.
authors.forename: Fabrice
authors.initials: F
authors.lastname: Lalloué
authors.affiliation: EA3842 Homéostasie Cellulaire et Pathologies and Chaire de Pneumologie Expérimentale, Université de Limoges, Faculté de Médecine, 2 Rue du Dr Raymond Marcland, 87025 Limoges CEDEX-France.
authors.forename: Marie-Odile
authors.initials: MO
authors.lastname: Jauberteau
mesh_terms: D033942:Adaptor Proteins, Vesicular Transport / Q000235:genetics / Q000378:metabolism*; D045744:Cell Line, Tumor; D002465:Cell Movement; D042783:Endothelial Cells / Q000201:enzymology / Q000378:metabolism; D066246:ErbB Receptors / Q000235:genetics / Q000378:metabolism*; D055354:Exosomes / Q000201:enzymology / Q000378:metabolism*; D006801:Humans; D008562:Membrane Glycoproteins / Q000235:genetics / Q000378:metabolism*; D011485:Protein Binding; D011505:Protein-Tyrosine Kinases / Q000235:genetics / Q000378:metabolism*; D020813:Receptor, trkB; D015398:Signal Transduction; D000099183:Sortilin
chemical_list: D033942:Adaptor Proteins, Vesicular Transport; D066246:ErbB Receptors; D008562:Membrane Glycoproteins; D011505:Protein-Tyrosine Kinases; D020813:Receptor, trkB; D000099183:Sortilin; C512478:EGFR protein, human; C000591259:tropomyosin-related kinase-B, human
keywords: Angiogenesis; Cancer; EGFR; Exosome; NTRK2; Sortilin; TrkB