Oncotarget

Research Papers:

Myoferlin is a novel exosomal protein and functional regulator of cancer-derived exosomes

Arnaud Blomme, Karim Fahmy, Olivier Peulen, Brunella Costanza, Marie Fontaine, Ingrid Struman, Dominique Baiwir, Edwin de Pauw, Marc Thiry, Akeila Bellahc√®ne, Vincent Castronovo and Andrei Turtoi _

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Oncotarget. 2016; 7:83669-83683. https://doi.org/10.18632/oncotarget.13276

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Abstract

Arnaud Blomme1, Karim Fahmy1, Olivier Peulen1, Brunella Costanza1, Marie Fontaine2, Ingrid Struman2, Dominique Baiwir3,4, Edwin de Pauw3, Marc Thiry5, Akeila Bellahcène1, Vincent Castronovo1,*, Andrei Turtoi1,3,*

1Metastasis Research Laboratory, GIGA Cancer, University of Liège, Liège, 4000, Belgium

2Molecular Angiogenesis Laboratory, GIGA Research, University of Liège, Liège, 4000, Belgium

3Laboratory of Mass Spectrometry, GIGA Research, University of Liège, Liège, 4000, Belgium

4GIGA Proteomics Facility, University of Liège, Liège, 4000, Belgium

5Laboratory of Cell Biology, Faculty of Sciences, University of Liège, Liège, 4000, Belgium

*These authors have contributed equally to this work

Correspondence to:

Andrei Turtoi, email: a.turtoi@ulg.ac.be

Keywords: proteomics, vesicle trafficking, angiogenesis, endothelial cells

Received: May 05, 2016    Accepted: October 06, 2016    Published: November 10, 2016

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.


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