title: Expression of myoferlin in human and murine carcinoma tumors: role in membrane repair, cell proliferation, and tumorigenesis.
abstract: Cancer cells are often characterized by high proliferation rates, a consequence of increased mitotic signaling coupled with unchecked cellular growth. We recently demonstrated that vascular endothelial cells unexpectedly express ferlins, a family of muscle-specific proteins capable of regulating the fusion of lipid patches to the plasma membrane, and that these highly regulated membrane fusion events are essential to endothelial cell proliferation and homeostasis. Here, we show that human and mouse breast cancer cell lines also express myoferlin at various levels, and that the processes of transformation, epithelial-mesenchymal transition, and metastasis do not appear to have any effect on myoferlin expression in vitro. In vivo, we observed that solid mouse and human carcinoma tissues also express high levels of myoferlin protein. Loss-of-function studies performed in mice revealed that myoferlin gene knockdown can attenuate cancer cell proliferation in vitro and decrease tumor burden, and that accelerated tumor cell growth appears to rely on intact myoferlin-dependent membrane repair and signaling under exponential growth conditions. To our knowledge, these data provide the first evidence of myoferlin expression in solid human and mouse tumors. We have thus identified a novel membrane repair process that likely helps sustain the high growth rates characteristic of tumors, and we suggest that interfering with normal myoferlin expression and/or membrane repair and remodeling may provide therapeutically relevant antiproliferative effects.
authors.affiliation: Providence Institute for Heart + Lung Health, James Hogg Research Centre, University of British Columbia, Vancouver, British Columbia, Canada.
authors.forename: Cleo
authors.initials: C
authors.lastname: Leung
authors.forename: Carol
authors.initials: C
authors.lastname: Yu
authors.forename: Michelle I
authors.initials: MI
authors.lastname: Lin
authors.forename: Cristina
authors.initials: C
authors.lastname: Tognon
authors.forename: Pascal
authors.initials: P
authors.lastname: Bernatchez
mesh_terms: D000368:Aged; D000818:Animals; D002135:Calcium-Binding Proteins / Q000378:metabolism*; D063646:Carcinogenesis / Q000378:metabolism* / Q000473:pathology*; D002277:Carcinoma / Q000098:blood supply / Q000378:metabolism* / Q000473:pathology*; D045744:Cell Line, Tumor; D002462:Cell Membrane / Q000378:metabolism / Q000473:pathology*; D049109:Cell Proliferation; D005260:Female; D055785:Gene Knockdown Techniques; D006801:Humans; D008565:Membrane Proteins / Q000378:metabolism*; D051379:Mice; D009124:Muscle Proteins / Q000378:metabolism*
chemical_list: D002135:Calcium-Binding Proteins; C415584:MYOF protein, human; D008565:Membrane Proteins; D009124:Muscle Proteins; C521810:myoferlin protein, mouse