1. A specific lipid metabolic profile is associated with the epithelial mesenchymal transition program
- Author
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Francesco De Nuccio, Angelo Santino, Loredana Capobianco, Stefania De Domenico, Michele Maffia, Isabelle Fournier, Antonio Gaballo, Anna Maria Giudetti, Michel Salzet, Pasquale Simeone, Julien Franck, Giuseppe Nicolardi, Paola Lanuti, Paola Lunetti, Andrea Ragusa, Daniele Vergara, University of Salento [Lecce], Biotecgen [Lecce, Italy], Department of Biological and Environmental Sciences and Technologies [Lecce, Italy], CNR NANOTEC - Institute of Nanotechnology [Lecce, Italy], Protéomique, Réponse Inflammatoire, Spectrométrie de Masse (PRISM) - U 1192 (PRISM), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Università degli studi 'G. d'Annunzio' Chieti-Pescara [Chieti-Pescara] (Ud'A), Giudetti, A, De Domenico, S., Ragusa, A., Lunetti, P., Gaballo, A., Franck, J., Simeone, P., Nicolardi, G., De Nuccio, F., Santino, A., Capobianco, L., Lanuti, P., Fournier, I., Salzet, M., Maffia, M., Vergara, D., Université de Lille-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), and SALZET, Michel
- Subjects
Proteomics ,0301 basic medicine ,Epithelial-Mesenchymal Transition ,β-Catenin ,[SDV]Life Sciences [q-bio] ,Breast Neoplasms ,Carbohydrate metabolism ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,Cell Line, Tumor ,Lipid droplet ,Humans ,Epithelial–mesenchymal transition ,Molecular Biology ,Phospholipids ,Triglycerides ,beta Catenin ,Fatty acid synthesis ,chemistry.chemical_classification ,Mass spectrometry ,Chemistry ,Lipogenesis ,Fatty Acids ,Lipid metabolism ,Cell Biology ,Metabolism ,Lipid Metabolism ,Lipids ,[SDV] Life Sciences [q-bio] ,Gene Expression Regulation, Neoplastic ,030104 developmental biology ,Biochemistry ,030220 oncology & carcinogenesis ,Metabolome ,Cadherin ,epithelial-to-mesenchymal transition ,Transcriptome ,Epithelial mesenchymal transition ,Polyunsaturated fatty acid - Abstract
International audience; 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.
- Published
- 2019
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