Decreasing stearoyl‐ C o A desaturase‐1 expression inhibits β‐catenin signaling in breast cancer cells

• Published in: Cancer science 2013-01, Vol.104 (1), p.36-42
• Main Authors: Mauvoisin, Daniel, Charfi, Cyndia, Lounis, Amine M, Rassart, Eric, Mounier, Catherine
• Format: Article
• Language: English
• ISSN: 1347-9032; 1349-7006
• DOI: 10.1111/cas.12032

Stearoyl‐ C o A desaturase‐1 ( SCD 1) is an endoplasmic reticulum anchored enzyme catalyzing the synthesis of monounsaturated fatty acids, mainly palmytoleyl‐ C o A and oleyl‐ C o A . Recent studies have revealed a function for SCD 1 in the modulation of signaling processes related to cell proliferation, survival and transformation to cancer. We used MCF 7 and MDA ‐ MB ‐231 cells to analyze the role of SCD 1 in the metastatic acquisition of breast cancer cells. Silencing SCD 1 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 ERK 1/2 MAPK are significantly reduced. Decreasing SCD 1 expression also reduces the level of GSK 3 phosphorylation, indicating higher activity of the kinase. Using cells fractionation, immunofluorescence and a β‐catenin/ TCF ‐responsive reporter construct, we demonstrate that lowering SCD 1 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 SCD 1 si RNA show a lower invasive potential than the control cells. Taken together, our data demonstrate that low SCD 1 expression is associated with a decrease in the proliferation rate of breast cancer cells associated with a decrease in ERK 1/2 activation. SCD 1 silencing also inhibits GSK 3 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 SCD 1 impairs the epithelial to mesenchymal transition‐like behavior of the cells, a characteristic of metastatic breast cancer. ( Cancer Sci 2013; 104: 36–42)