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

Anna Maria Giudetti, Stefania De Domenico, Andrea Ragusa, Paola Lunetti, Antonio Gaballo, Julien Franck, Pasquale Simeone, Giuseppe Nicolardi, Francesco De Nuccio, Angelo Santino, Loredana Capobianco, Paola Lanuti, Isabelle Fournier, Michel Salzet, Michele Maffia, Daniele Vergara,

Biochim Biophys Acta Mol Cell Biol Lipids

https://doi.org/10.1016/j.bbalip.2018.12.011

Abstract

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.