title: Myoferlin is a key regulator of EGFR activity in breast cancer.
abstract: Myoferlin is a member of the ferlin family of proteins that participate in plasma membrane fusion, repair, and endocytosis. While some reports have implicated myoferlin in cancer, the extent of its expression in and contributions to cancer are not well established. In this study, we show that myoferlin is overexpressed in human breast cancers and that it has a critical role in controlling degradation of the epidermal growth factor (EGF) receptor (EGFR) after its activation and internalization in breast cancer cells. Myoferlin depletion blocked EGF-induced cell migration and epithelial-to-mesenchymal transition. Both effects were induced as a result of impaired degradation of phosphorylated EGFR via dysfunctional plasma membrane caveolae and alteration of caveolin homo-oligomerization. In parallel, myoferlin depletion reduced tumor development in a chicken chorioallantoic membrane xenograft model of human breast cancer. Considering the therapeutic significance of EGFR targeting, our findings identify myoferlin as a novel candidate function to target for future drug development.
authors.affiliation: Metastasis Research Laboratory, GIGA Cancer, University of Liège, Liège, Belgium. a.turtoi@ulg.ac.be
authors.forename: Andrei
authors.initials: A
authors.lastname: Turtoi
authors.forename: Arnaud
authors.initials: A
authors.lastname: Blomme
authors.forename: Akeila
authors.initials: A
authors.lastname: Bellahcène
authors.forename: Christine
authors.initials: C
authors.lastname: Gilles
authors.forename: Vincent
authors.initials: V
authors.lastname: Hennequière
authors.forename: Paul
authors.initials: P
authors.lastname: Peixoto
authors.forename: Elettra
authors.initials: E
authors.lastname: Bianchi
authors.forename: Agnès
authors.initials: A
authors.lastname: Noel
authors.forename: Edwin
authors.initials: E
authors.lastname: De Pauw
authors.forename: Eric
authors.initials: E
authors.lastname: Lifrange
authors.forename: Philippe
authors.initials: P
authors.lastname: Delvenne
authors.forename: Vincent
authors.initials: V
authors.lastname: Castronovo
mesh_terms: D000230:Adenocarcinoma / Q000378:metabolism / Q000473:pathology; D000818:Animals; D017209:Apoptosis; D001943:Breast Neoplasms / Q000378:metabolism / Q000473:pathology*; D002135:Calcium-Binding Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D018270:Carcinoma, Ductal, Breast / Q000378:metabolism / Q000473:pathology*; D018275:Carcinoma, Lobular / Q000378:metabolism / Q000473:pathology*; D021941:Caveolae / Q000378:metabolism; D002465:Cell Movement; D049109:Cell Proliferation; D002642:Chick Embryo; D049033:Chorioallantoic Membrane / Q000378:metabolism; D004815:Epidermal Growth Factor / Q000494:pharmacology; D058750:Epithelial-Mesenchymal Transition; D066246:ErbB Receptors / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D005260:Female; D005455:Fluorescent Antibody Technique; D015972:Gene Expression Regulation, Neoplastic; D006019:Glycolysis; D006801:Humans; D007124:Immunoenzyme Techniques; D008565:Membrane Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D009124:Muscle Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D009361:Neoplasm Invasiveness; D040901:Proteomics; D034741:RNA, Small Interfering / Q000235:genetics; D014407:Tumor Cells, Cultured
chemical_list: D002135:Calcium-Binding Proteins; C415584:MYOF protein, human; D008565:Membrane Proteins; D009124:Muscle Proteins; D034741:RNA, Small Interfering; D004815:Epidermal Growth Factor; C512478:EGFR protein, human; D066246:ErbB Receptors