title: Sef Regulates Epithelial-Mesenchymal Transition in Breast Cancer Cells.
abstract: Sef (similar expression to fgf), also know as IL17RD, is a transmembrane protein shown to inhibit fibroblast growth factor signaling in developmental and cancer contexts; however, its role as a tumor suppressor remains to be fully elucidated. Here, we show that Sef regulates epithelial-mesenchymal transition (EMT) in breast cancer cell lines. Sef expression was highest in the normal breast epithelial cell line MCF10A, intermediate expression in MCF-7 cells and lowest in MDA-MB-231 cells. Knockdown of Sef increased the expression of genes associated with EMT, and promoted cell migration, invasion, and a fibroblastic morphology of MCF-7 cells. Overexpression of Sef inhibited the expression of EMT marker genes and inhibited cell migration and invasion in MCF-7 cells. Induction of EMT in MCF10A cells by TGF-β and TNF-α resulted in downregulation of Sef expression concomitant with upregulation of EMT gene expression and loss of epithelial morphology. Overexpression of Sef in MCF10A cells partially blocked cytokine-induced EMT. Sef was shown to block β-catenin mediated luciferase reporter activity and to cause a decrease in the nuclear localization of active β-catenin. Furthermore, Sef was shown to co-immunoprecipitate with β-catenin. In a mouse orthotopic xenograft model, Sef overexpression in MDA-MB-231 cells slowed tumor growth and reduced expression of EMT marker genes. Together, these data indicate that Sef plays a role in the negative regulation of EMT in a β-catenin dependent manner and that reduced expression of Sef in breast tumor cells may be permissive for EMT and the acquisition of a more metastatic phenotype. J. Cell. Biochem. 117: 2346-2356, 2016. © 2016 Wiley Periodicals, Inc.
authors.affiliation: Center for Molecular Medicine, Maine Medical Center Research Institute, Scarborough, Maine.|Graduate School for Biomedical Sciences and Engineering, University of Maine, Orono, Maine.
authors.forename: Qing
authors.initials: Q
authors.lastname: He
authors.affiliation: Center for Molecular Medicine, Maine Medical Center Research Institute, Scarborough, Maine.|Graduate School for Biomedical Sciences and Engineering, University of Maine, Orono, Maine.
authors.forename: Yan
authors.initials: Y
authors.lastname: Gong
authors.affiliation: Center for Molecular Medicine, Maine Medical Center Research Institute, Scarborough, Maine.
authors.forename: Lindsey
authors.initials: L
authors.lastname: Gower
authors.affiliation: Center for Molecular Medicine, Maine Medical Center Research Institute, Scarborough, Maine.
authors.forename: Xuehui
authors.initials: X
authors.lastname: Yang
authors.affiliation: Center for Molecular Medicine, Maine Medical Center Research Institute, Scarborough, Maine.|Graduate School for Biomedical Sciences and Engineering, University of Maine, Orono, Maine.
authors.forename: Robert E
authors.initials: RE
authors.lastname: Friesel
mesh_terms: D000818:Animals; D017209:Apoptosis; D015153:Blotting, Western; D001943:Breast Neoplasms / Q000378:metabolism / Q000473:pathology*; D002465:Cell Movement; D049109:Cell Proliferation; D058750:Epithelial-Mesenchymal Transition; D005260:Female; D005455:Fluorescent Antibody Technique; D006801:Humans; D047468:Immunoprecipitation; D051379:Mice; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D018123:Receptors, Interleukin / Q000378:metabolism*; D014407:Tumor Cells, Cultured
chemical_list: C477526:IL17RD protein, human; D018123:Receptors, Interleukin
keywords: BREAST CANCER; EPITHELIAL MESENCHYMAL TRANSITION; MIGRATION; SEF; SLUG; SNAIL