Myoferlin plays a key role in VEGFA secretion and impacts tumor-associated angiogenesis in human pancreas cancer

Karim Fahmy, Arnaud Gonzalez, Mohammad Arafa, Paul Peixoto, Akeila Bellahcène, Andrei Turtoi, Philippe Delvenne, Marc Thiry, Vincent Castronovo, Olivier Peulen

Research output: Contribution to journalArticlepeer-review

45 Citations (Scopus)


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.

Original languageEnglish
Pages (from-to)652-63
Number of pages12
JournalInternational Journal of Cancer
Issue number3
Publication statusPublished - Feb 1 2016


  • Adenocarcinoma/blood supply
  • Calcium-Binding Proteins/analysis
  • Carcinoma, Pancreatic Ductal/blood supply
  • Cell Line, Tumor
  • Cell Proliferation
  • Humans
  • Membrane Proteins/analysis
  • Muscle Proteins/analysis
  • Neovascularization, Pathologic/etiology
  • Pancreatic Neoplasms/blood supply
  • Platelet Endothelial Cell Adhesion Molecule-1/analysis
  • Vascular Endothelial Growth Factor A/analysis

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