Abstract :
[en] 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, toensure 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 environmentThe 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 suggestthat 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 tumorvolumes 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 andpancreatic cancer cell-derived exosomes. We prove that myoferlin is expressed on the outersurface 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 sodecreases 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 tonormal counterparts. Overall, myoferlin plays a role in exosome functions, as myoferlin-depletedexosomes are able to mediate less phenotypic changes in HUVEC cells.
