title: Myoferlin is a novel exosomal protein and functional regulator of cancer-derived exosomes.
abstract: Exosomes are communication mediators participating in the intercellular exchange of proteins, metabolites and nucleic acids. Recent studies have demonstrated that exosomes are characterized by a unique proteomic composition that is distinct from the cellular one. The mechanisms responsible for determining the proteome content of the exosomes remain however obscure. In the current study we employ ultrastructural approach to validate a novel exosomal protein myoferlin. This is a multiple C2-domain containing protein, known for its conserved physiological function in endocytosis and vesicle fusion biology. Emerging studies demonstrate that myoferlin is frequently overexpressed in cancer, where it promotes cancer cell migration and invasion. Our data expand these findings by showing that myoferlin is a general component of cancer cell derived exosomes from different breast and pancreatic cancer cell lines. Using proteomic analysis, we demonstrate for the first time that myoferlin depletion in cancer cells leads to a significantly modulated exosomal protein load. Such myoferlin-depleted exosomes were also functionally deficient as shown by their reduced capacity to transfer nucleic acids to human endothelial cells (HUVEC). Beyond this, myoferlin-depleted cancer exosomes also had a significantly reduced ability to induce migration and proliferation of HUVEC. The present study highlights myoferlin as a new functional player in exosome biology, calling for novel strategies to target this emerging oncogene in human cancer.
authors.affiliation: Metastasis Research Laboratory, GIGA Cancer, University of Liège, Liège, 4000, Belgium.
authors.forename: Arnaud
authors.initials: A
authors.lastname: Blomme
authors.affiliation: Metastasis Research Laboratory, GIGA Cancer, University of Liège, Liège, 4000, Belgium.
authors.forename: Karim
authors.initials: K
authors.lastname: Fahmy
authors.affiliation: Metastasis Research Laboratory, GIGA Cancer, University of Liège, Liège, 4000, Belgium.
authors.forename: Olivier
authors.initials: O
authors.lastname: Peulen
authors.affiliation: Metastasis Research Laboratory, GIGA Cancer, University of Liège, Liège, 4000, Belgium.
authors.forename: Brunella
authors.initials: B
authors.lastname: Costanza
authors.affiliation: Molecular Angiogenesis Laboratory, GIGA Research, University of Liège, Liège, 4000, Belgium.
authors.forename: Marie
authors.initials: M
authors.lastname: Fontaine
authors.affiliation: Molecular Angiogenesis Laboratory, GIGA Research, University of Liège, Liège, 4000, Belgium.
authors.forename: Ingrid
authors.initials: I
authors.lastname: Struman
authors.affiliation: Laboratory of Mass Spectrometry, GIGA Research, University of Liège, Liège, 4000, Belgium.|GIGA Proteomics Facility, University of Liège, Liège, 4000, Belgium.
authors.forename: Dominique
authors.initials: D
authors.lastname: Baiwir
authors.affiliation: Laboratory of Mass Spectrometry, GIGA Research, University of Liège, Liège, 4000, Belgium.
authors.forename: Edwin
authors.initials: E
authors.lastname: de Pauw
authors.affiliation: Laboratory of Cell Biology, Faculty of Sciences, University of Liège, Liège, 4000, Belgium.
authors.forename: Marc
authors.initials: M
authors.lastname: Thiry
authors.affiliation: Metastasis Research Laboratory, GIGA Cancer, University of Liège, Liège, 4000, Belgium.
authors.forename: Akeila
authors.initials: A
authors.lastname: Bellahcène
authors.affiliation: Metastasis Research Laboratory, GIGA Cancer, University of Liège, Liège, 4000, Belgium.
authors.forename: Vincent
authors.initials: V
authors.lastname: Castronovo
authors.affiliation: Metastasis Research Laboratory, GIGA Cancer, University of Liège, Liège, 4000, Belgium.|Laboratory of Mass Spectrometry, GIGA Research, University of Liège, Liège, 4000, Belgium.
authors.forename: Andrei
authors.initials: A
authors.lastname: Turtoi
mesh_terms: D015153:Blotting, Western; D001943:Breast Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000648:ultrastructure; D002135:Calcium-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D002465:Cell Movement; D049109:Cell Proliferation; D055354:Exosomes / Q000235:genetics / Q000378:metabolism* / Q000648:ultrastructure; D005260:Female; D061307:Human Umbilical Vein Endothelial Cells / Q000378:metabolism; D006801:Humans; D061986:MCF-7 Cells; D008297:Male; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D008854:Microscopy, Electron; D009124:Muscle Proteins / Q000235:genetics / Q000378:metabolism*; D018919:Neovascularization, Physiologic; D010190:Pancreatic Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000648:ultrastructure; D060066:Protein Interaction Maps; D040901:Proteomics / Q000379:methods; D034622:RNA Interference; D015398:Signal Transduction; D014162:Transfection
chemical_list: D002135:Calcium-Binding Proteins; C415584:MYOF protein, human; D008565:Membrane Proteins; D009124:Muscle Proteins
keywords: angiogenesis; endothelial cells; proteomics; vesicle trafficking