title: Decreasing stearoyl-CoA desaturase-1 expression inhibits β-catenin signaling in breast cancer cells.
abstract: Stearoyl-CoA desaturase-1 (SCD1) is an endoplasmic reticulum anchored enzyme catalyzing the synthesis of monounsaturated fatty acids, mainly palmytoleyl-CoA and oleyl-CoA. Recent studies have revealed a function for SCD1 in the modulation of signaling processes related to cell proliferation, survival and transformation to cancer. We used MCF7 and MDA-MB-231 cells to analyze the role of SCD1 in the metastatic acquisition of breast cancer cells. Silencing SCD1 expression in breast cancer cells has no effect on cell viability but the levels of cell proliferation, cell cycle genes' expressions and the phosphorylation state of ERK1/2 MAPK are significantly reduced. Decreasing SCD1 expression also reduces the level of GSK3 phosphorylation, indicating higher activity of the kinase. Using cells fractionation, immunofluorescence and a β-catenin/TCF-responsive reporter construct, we demonstrate that lowering SCD1 expression leads to a decrease of β-catenin amounts within the nucleus and to inhibition of its transactivation capacity. Moreover, MDA-MB-231 cells transfected with the SCD1 siRNA show a lower invasive potential than the control cells. Taken together, our data demonstrate that low SCD1 expression is associated with a decrease in the proliferation rate of breast cancer cells associated with a decrease in ERK1/2 activation. SCD1 silencing also inhibits GSK3 phosphorylation, lowering β-catenin translocation to the nucleus, and, subsequently, its transactivation capacity and the expression of its target genes. Finally, we show that silencing SCD1 impairs the epithelial to mesenchymal transition-like behavior of the cells, a characteristic of metastatic breast cancer.
authors.affiliation: BioMed, Department of Biological Science, University of Quebec, Montreal, Canada.
authors.forename: Daniel
authors.initials: D
authors.lastname: Mauvoisin
authors.forename: Cyndia
authors.initials: C
authors.lastname: Charfi
authors.forename: Amine M
authors.initials: AM
authors.lastname: Lounis
authors.forename: Eric
authors.initials: E
authors.lastname: Rassart
authors.forename: Catherine
authors.initials: C
authors.lastname: Mounier
mesh_terms: D001943:Breast Neoplasms / Q000378:metabolism* / Q000473:pathology; D002453:Cell Cycle; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D002470:Cell Survival; D002471:Cell Transformation, Neoplastic; D004721:Endoplasmic Reticulum / Q000201:enzymology; D058750:Epithelial-Mesenchymal Transition / Q000235:genetics; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D005229:Fatty Acids, Monounsaturated / Q000378:metabolism; D005260:Female; D038341:Glycogen Synthase Kinases / Q000378:metabolism; D006801:Humans; D061986:MCF-7 Cells; D009361:Neoplasm Invasiveness; D010766:Phosphorylation; D034622:RNA Interference; D034741:RNA, Small Interfering; D015398:Signal Transduction; D013230:Stearoyl-CoA Desaturase / Q000235:genetics / Q000378:metabolism*; D051176:beta Catenin / Q000378:metabolism*
chemical_list: D005229:Fatty Acids, Monounsaturated; D034741:RNA, Small Interfering; D051176:beta Catenin; D013230:Stearoyl-CoA Desaturase; D038341:Glycogen Synthase Kinases; D048049:Extracellular Signal-Regulated MAP Kinases