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Si us plau utilitzeu sempre aquest identificador per citar o enllaçar aquest document: https://hdl.handle.net/2445/121900
Model-driven discovery of long-chain fatty acid metabolic reprogramming in heterogeneous prostate cancer cells.
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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.
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MARÍN DE MAS, Igor bartolomé, AGUILAR FADÓ, Esther, ZODDA, Erika, BALCELLS NADAL, Cristina, MARÍN MARTÍNEZ, Silvia, DALLMANN, Guido, THOMSON, Timothy m., PAPP, Balázs, CASCANTE I SERRATOSA, Marta. Model-driven discovery of long-chain fatty acid metabolic reprogramming in heterogeneous prostate cancer cells.. _PLoS Computational Biology_. 2018. Vol. 14, núm. 1, pàgs. e1005914. [consulta: 26 de febrer de 2026]. ISSN: 1553-734X. [Disponible a: https://hdl.handle.net/2445/121900]