title: Myoferlin depletion in breast cancer cells promotes mesenchymal to epithelial shape change and stalls invasion.
abstract: Myoferlin (MYOF) is a mammalian ferlin protein with homology to ancestral Fer-1, a nematode protein that regulates spermatic membrane fusion, which underlies the amoeboid-like movements of its sperm. Studies in muscle and endothelial cells have reported on the role of myoferlin in membrane repair, endocytosis, myoblast fusion, and the proper expression of various plasma membrane receptors. In this study, using an in vitro human breast cancer cell model, we demonstrate that myoferlin is abundantly expressed in invasive breast tumor cells. Depletion of MYOF using lentiviral-driven shRNA expression revealed that MDA-MB-231 cells reverted to an epithelial morphology, suggesting at least some features of mesenchymal to epithelial transition (MET). These observations were confirmed by the down-regulation of some mesenchymal cell markers (e.g., fibronectin and vimentin) and coordinate up-regulation of the E-cadherin epithelial marker. Cell invasion assays using Boyden chambers showed that loss of MYOF led to a significant diminution in invasion through Matrigel or type I collagen, while cell migration was unaffected. PCR array and screening of serum-free culture supernatants from shRNA(MYOF) transduced MDA-MB-231 cells indicated a significant reduction in the steady-state levels of several matrix metalloproteinases. These data when considered in toto suggest a novel role of MYOF in breast tumor cell invasion and a potential reversion to an epithelial phenotype upon loss of MYOF.
authors: Laboratory of Perinatal Research, Division of Maternal-Fetal Medicine, Department of Obstetrics and Gynecology, The Ohio State University, Columbus, Ohio, United States of America.
authors: Ruth
authors: R
authors: Li
authors: William E
authors: WE
authors: Ackerman
authors: Cosmin
authors: C
authors: Mihai
authors: Leonithas I
authors: LI
authors: Volakis
authors: Samir
authors: S
authors: Ghadiali
authors: Douglas A
authors: DA
authors: Kniss
mesh_terms: D002135:Calcium-Binding Proteins / Q000235:genetics / Q000502:physiology*; D045744:Cell Line, Tumor; D048430:Cell Shape; D058750:Epithelial-Mesenchymal Transition; D005260:Female; D055785:Gene Knockdown Techniques; D006801:Humans; D020782:Matrix Metalloproteinases / Q000378:metabolism; D008565:Membrane Proteins / Q000235:genetics / Q000502:physiology*; D009124:Muscle Proteins / Q000235:genetics / Q000502:physiology*; D009361:Neoplasm Invasiveness
chemical_list: D002135:Calcium-Binding Proteins; C415584:MYOF protein, human; D008565:Membrane Proteins; D009124:Muscle Proteins; D020782:Matrix Metalloproteinases