Article (Scientific journals)
Myoferlin is a novel exosomal protein and functional regulator of cancer-derived exosomes
Blomme, Arnaud; Fahmy, Karim; Peulen, Olivier et al.
2016In Oncotarget
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Keywords :
proteomics; vesicle trafficking; endothelial cells; angiogenesis
Abstract :
[en] 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 ndings 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 rst time that myoferlin depletion in cancer cells leads to a signi cantly modulated exosomal protein load. Such myoferlin-depleted exosomes were also functionally de cient as shown by their reduced capacity to transfer nucleic acids to human endothelial cells (HUVEC). Beyond this, myoferlin-depleted cancer exosomes also had a signi cantly 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.
Disciplines :
Oncology
Author, co-author :
Blomme, Arnaud  
Fahmy, Karim
Peulen, Olivier  ;  Université de Liège > Département des sciences biomédicales et précliniques > Département des sciences biomédicales et précliniques
Costanza, Brunella ;  Université de Liège - ULiège > Doct. sc. bioméd. & pharma. (paysage)
Fontaine, Marie ;  Université de Liège > Département des sciences de la vie > GIGA-R : Biologie et génétique moléculaire
Struman, Ingrid  ;  Université de Liège > Département des sciences de la vie > GIGA-R : Biologie et génétique moléculaire
Baiwir, Dominique  ;  Université de Liège > GIGA-Technology platforms : Plate-forme protéomique
De Pauw, Edwin  ;  Université de Liège > Département de chimie (sciences) > Laboratoire de spectrométrie de masse (L.S.M.)
Thiry, Marc  ;  Université de Liège > Département des sciences de la vie > GIGA-R : Biologie cellulaire
Bellahcene, Akeila ;  Université de Liège > Département des sciences biomédicales et précliniques > GIGA-R : Labo de recherche sur les métastases
Castronovo, Vincenzo  ;  Université de Liège > Département des sciences biomédicales et précliniques > Biologie générale et cellulaire
Turtoi, Andrei  ;  Université de Liège > Département des sciences biomédicales et précliniques > GIGA-R : Labo de recherche sur les métastases
 These authors have contributed equally to this work.
Language :
English
Title :
Myoferlin is a novel exosomal protein and functional regulator of cancer-derived exosomes
Publication date :
10 November 2016
Journal title :
Oncotarget
eISSN :
1949-2553
Publisher :
Impact Journals, Albany, United States - New York
Peer reviewed :
Peer Reviewed verified by ORBi
Funders :
F.R.S.-FNRS - Fonds de la Recherche Scientifique [BE]
Télévie [BE]
CAC - Centre anticancéreux près l'Université de Liège asbl [BE]
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