A specific lipid metabolic profile is associated with the epithelial mesenchymal transition program

• Published in: Biochimica et biophysica acta. Molecular and cell biology of lipids 2019-03, Vol.1864 (3), p.344-357
• Main Authors: Giudetti, Anna Maria, De Domenico, Stefania, Ragusa, Andrea, Lunetti, Paola, Gaballo, Antonio, Franck, Julien, Simeone, Pasquale, Nicolardi, Giuseppe, De Nuccio, Francesco, Santino, Angelo, Capobianco, Loredana, Lanuti, Paola, Fournier, Isabelle, Salzet, Michel, Maffia, Michele, Vergara, Daniele
• Format: Article
• Language: English
• Subjects: Epithelial mesenchymal transition; Life Sciences; Lipids; Mass spectrometry; Metabolism; β-Catenin
• ISSN: 1388-1981; 1879-2618
• DOI: 10.1016/j.bbalip.2018.12.011

Several studies have identified a specific metabolic program that is associated with the process of epithelial-mesenchymal transition (EMT). Whereas much is known about the association between glucose metabolism and EMT, the contribution of lipid metabolism is not still completely understood. Here, we studied epithelial and mesenchymal breast cancer cells by proteomic and lipidomic approaches and identified significant differences that characterised these models concerning specific metabolic enzymes and metabolites including fatty acids and phospholipids. Higher levels of monounsaturated fatty acids together with increased expression of enzymes of de novo fatty acid synthesis is the distinct signature of epithelial with respect to mesenchymal cells that, on the contrary, show reduced lipogenesis, higher polyunsaturated fatty acids level and increased expression of genes involved in the triacylglycerol (TAG) synthesis and lipid droplets formation. In the mesenchymal model, the diacylglycerol acyltransferase (DGAT)-1 appears to be the major enzyme involved in TAG synthesis and inhibition of DGAT1, but not DGAT2, drastically reduces the incorporation of labeled palmitate into TAG. Moreover, knockdown of β-catenin demonstrated that this metabolic phenotype in under the control of a network of transcriptional factors and that β-catenin has a specific role in the regulation of lipid metabolism in mesenchymal cells. •This study aims to demonstrate the different metabolic profile of epithelial and mesenchymal breast cancer models.•Our results identify a number of differentially expressed enzymes related to lipid metabolism.•Knockdown of β-catenin affects the expression of lipid metabolic genes in the mesenchymal model.