Título:
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Model-driven discovery of long-chain fatty acid metabolic reprogramming in heterogeneous prostate cancer cells.
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Autor/a:
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Marín de Mas, Igor Bartolomé; Aguilar Fadó, Esther; Zodda, Erika; Balcells, Cristina; Marín Martínez, Silvia; Dallmann, Guido; Thomson, Timothy M.; Papp, Balázs; Cascante i Serratosa, Marta
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Otros autores:
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Universitat de Barcelona |
Abstract:
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Epithelial-mesenchymal-transition promotes intra-tumoral heterogeneity, by enhancing tumor cell invasiveness and promoting drug resistance. We integrated transcriptomic data for two clonal subpopulations from a prostate cancer cell line (PC-3) into a genome-scale metabolic network model to explore their metabolic differences and potential vulnerabilities. In this dual cell model, PC-3/S cells express Epithelial-mesenchymal-transition markers and display high invasiveness and low metastatic potential, while PC-3/M cells present the opposite phenotype and higher proliferative rate. Model-driven analysis and experimental validations unveiled a marked metabolic reprogramming in long-chain fatty acids metabolism. While PC-3/M cells showed an enhanced entry of long-chain fatty acids into the mitochondria, PC-3/S cells used long-chain fatty acids as precursors of eicosanoid metabolism. We suggest that this metabolic reprogramming endows PC-3/M cells with augmented energy metabolism for fast proliferation and PC-3/S cells with increased eicosanoid production impacting angiogenesis, cell adhesion and invasion. PC-3/S metabolism also promotes the accumulation of docosahexaenoic acid, a long-chain fatty acid with antiproliferative effects. The potential therapeutic significance of our model was supported by a differential sensitivity of PC-3/M cells to etomoxir, an inhibitor of long-chain fatty acid transport to the mitochondria. |
Materia(s):
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-Cèl·lules canceroses -Càncer de pròstata -Metabolisme -Epiteli -Cancer cells -Prostate cancer -Metabolism -Epithelium |
Derechos:
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cc-by (c) Marin-de Mas, Igor et al., 2018
http://creativecommons.org/licenses/by/3.0/es |
Tipo de documento:
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Artículo Artículo - Versión publicada |
Editor:
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Public Library of Science (PLoS)
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