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Epitranscriptomics & Cancer Adaptation : A.David

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Our research work focuses on the contribution of post-transcriptional mechanisms on cancer cell adaptation, in particular RNA epigenetic & translational control.

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Group name EquipeAT
Item Type Journal Article
Title Myoferlin plays a key role in VEGFA secretion and impacts tumor-associated angiogenesis in human pancreas cancer
Creator Fahmy et al.
Author Karim Fahmy
Author Arnaud Gonzalez
Author Mohammad Arafa
Author Paul Peixoto
Author Akeila Bellahcène
Author Andrei Turtoi
Author Philippe Delvenne
Author Marc Thiry
Author Vincent Castronovo
Author Olivier Peulen
Abstract Pancreatic ductal adenocarcinoma is one of the most deadly forms of cancers with no satisfactory treatment to date. Recent studies have identified myoferlin, a ferlin family member, in human pancreas adenocarcinoma where its expression was associated to a bad prognosis. However, the function of myoferlin in pancreas adenocarcinoma has not been reported. In other cell types, myoferlin is involved in several key plasma membrane processes such as fusion, repair, endocytosis and tyrosine kinase receptor activity. In this study, we showed that myoferlin silencing in BxPC-3 human pancreatic cancer cells resulted in the inhibition of cell proliferation in vitro and in a significant reduction of the tumor volume in chick chorioallantoic membrane assay. In addition to be smaller, the tumors formed by the myoferlin-silenced cells showed a marked absence of functional blood vessels. We further demonstrated that this effect was due, at least in part, to an inhibition of VEGFA secretion by BxPC-3 myoferlin-silenced cells. Using immunofluorescence and electron microscopy, we linked the decreased VEGFA secretion to an impairment of VEGFA exocytosis. The clinical relevance of our results was further strengthened by a significant correlation between myoferlin expression in a series of human pancreatic malignant lesions and their angiogenic status evaluated by the determination of the blood vessel density.
Publication International Journal of Cancer
Volume 138
Issue 3
Pages 652-663
Date Feb 01, 2016
Journal Abbr Int. J. Cancer
Language eng
DOI 10.1002/ijc.29820
ISSN 1097-0215
Library Catalog PubMed
Extra PMID: 26311411
Tags Adenocarcinoma, angiogenesis, Calcium-Binding Proteins, Carcinoma, Pancreatic Ductal, Cell Line, Tumor, Cell Proliferation, exocytosis, Humans, Membrane Proteins, Muscle Proteins, myoferlin, Neovascularization, Pathologic, original, pancreas ductal adenocarcinoma, Pancreatic Neoplasms, Platelet Endothelial Cell Adhesion Molecule-1, Vascular Endothelial Growth Factor A, VEGF
Date Added 2019/05/29 - 14:23:39
Date Modified 2019/05/29 - 14:33:54
Notes and Attachments PubMed entry (Attachment)
Texte intégral (Attachment)


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