Decreasing stearoyl‐CoA desaturase‐1 expression inhibits β‐catenin signaling in breast cancer cells

Cancer Science - Tập 104 Số 1 - Trang 36-42 - 2013
Daniel Mauvoisin1, Cyndia Charfi1, Mohamed Amine Lounis1, Éric Rassart1, Cathérine Mounier1
1BioMed, Department of Biological Science University of Quebec Montreal Canada

Tóm tắt

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. (Cancer Sci 2013; 104: 36–42)

Từ khóa


Tài liệu tham khảo

10.1207/S15327914NC4501_1

10.1007/s00125-009-1300-4

10.1038/nutd.2011.19

Enoch HG, 1976, Mechanism of rat liver microsomal stearyl‐CoA desaturase Studies of the substrate specificity, enzyme‐substrate interactions, and the function of lipid, J Biol Chem, 251, 5095, 10.1016/S0021-9258(17)33223-4

10.1016/S0022-2275(20)40030-6

10.1007/BF01834624

Williams CM, 1993, Fatty acid compositions of inositol and choline phospholipids of breast tumours and normal breast tissue, Eur J Clin Nutr, 47, 260

10.1016/j.bbalip.2004.11.015

10.1371/journal.pone.0006812

10.1093/carcin/bgq131

10.1002/(SICI)1097-0215(19991126)83:5<585::AID-IJC2>3.0.CO;2-Z

10.1093/aje/kwn069

10.1093/jnci/93.14.1088

10.1136/bmj.311.7015.1251

10.1200/JCO.1997.15.4.1377

10.1080/01635589509514403

10.1093/ajcn/68.1.134

10.1016/j.molmed.2007.10.004

10.1007/s10555-008-9179-y

10.1146/annurev.cellbio.19.011102.111135

10.1101/gad.230302

10.1126/science.280.5363.596

10.1038/35035124

10.1126/science.275.5307.1784

10.1074/jbc.270.40.23589

10.1074/jbc.271.34.20608

10.4161/cc.2.4.433

10.1101/gad.12.22.3499

Scaglia N, 2008, Inhibition of Stearoyl‐CoA Desaturase 1 expression in human lung adenocarcinoma cells impairs tumorigenesis, Int J Oncol, 33, 839

Gilles C, 2003, Transactivation of vimentin by beta‐catenin in human breast cancer cells, Cancer Res, 63, 2658

10.1093/emboj/16.13.3797

10.1074/jbc.M111.322800

10.1016/j.jhep.2008.07.036

10.1158/0008-5472.CAN-06-4132

10.1371/journal.pone.0033823

10.1258/ebm.2011.010265

10.1152/ajpendo.00388.2010

10.1158/1535-7163.MCT-09-1064

10.1158/1541-7786.MCR-11-0126

10.1371/journal.pone.0011394

10.1186/1471-2407-9-325

10.1006/cbir.2002.0901

Logullo AF, 2010, Concomitant expression of epithelial–mesenchymal transition biomarkers in breast ductal carcinoma: association with progression, Oncol Rep, 23, 313

10.1073/pnas.060025397

10.1371/journal.pone.0004243

10.1016/j.devcel.2006.10.003

10.1128/MCB.7.2.725

Thông tin
Thông tin xuất bản

Cancer Science

Tập 104 Số 1

36-42

Thông tin tác giả