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Page de résumé pour ULgetd-10232016-133731

Auteur : Fahmy, Karim
E-mail de l'auteur : karime.soliman@gmail.com
URN : ULgetd-10232016-133731
Langue : Anglais/English
Titre : Contribution to the study of Myoferlin in Vesicle-Mediated Cancer Cellular Communication
Intitulé du diplôme : Doctorat en sciences biomédicales et pharmaceutiques
Département : Médecine - Département des sciences précliniques
Jury :
Nom : Titre :
DEROANNE, Christophe Membre du jury/Committee Member
DETRY, Olivier Membre du jury/Committee Member
NOEL, Agnès Membre du jury/Committee Member
PEIXOTO, Paul Membre du jury/Committee Member
SOMJA, Joan Membre du jury/Committee Member
VAN LAETHEM, Jean-Luc Membre du jury/Committee Member
DE PAUW, Marie-Claire Président du jury/Committee Chair
CASTRONOVO, Vincent Promoteur/Director
PEULEN, Olivier Promoteur/Director
Mots-clés :
  • Moyferlin
  • cellular communication
  • vesicles
  • exocytosis
  • exosomes
  • pancreas cancer
  • breast cancer
Date de soutenance : 2016-09-21
Type d'accès : Public/Internet
Résumé :

Cellular communication is a fundamental phenomenon in all multicellular organisms. All cells in a human body must communicate with each other’s to govern biological functions, to

ensure all processes from the development of an egg, to the survival, and to the reproduction.

In multicellular organisms, cell survival is dependent on the reception of information from their environment

The role of myoferlin, a muscle fusion protein, has been starting to get revealed in endothelial and muscle cells, showing an important implication in fusion, fission and endocytosis; thus there is an increasing interest in understanding its probable role in cancer progression.

Immunohistochemical evidences available from “Human Protein Atlas” database suggest

that myoferlin is strongly expressed in several cancer types including pancreas, stomach,

liver, colorectal, ovarian, cervical, endometrial, thyroid, breast and lung cancers.

In our study, we confirm myoferlin to be an important factor in PDAC progression. Myoferlin plays a role in tumor cell growth as well as VEGF-A mediated angiogenesis. Mechanistically, myoferlin plays a role in VEGF-A secretion without altering its transcription. Myoferlin seems to mediate VEGF-A secretory granules docking and fusion with the plasma membrane in order to secrete their cargo and to make the call for angiogenesis.

In vivo chicken chorioallantoic membrane model, myoferlin depletion reduced both tumor

volumes and tumor vascularization. On the patients level, myoferlin staining in PDAC sections correlates with both high MVD and poor survival.

We also report in here for the first time, that myoferlin is expressed in different breast and

pancreatic cancer cell-derived exosomes. We prove that myoferlin is expressed on the outer

surface of exosomes and is involved in the fusion and uptake of exosomes by HUVEC cells.

Myoferlin depletion of exosomes reduces uptake of exosomes by the target cells and so

decreases the cargo transfer into them. Myoferlin also plays a role in exosome biogenesis as myoferlin-depleted exosomes are smaller and harbor altered protein content compared to

normal counterparts.

Overall, myoferlin plays a role in exosome functions, as myoferlin-depleted

exosomes are able to mediate less phenotypic changes in HUVEC cells.

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