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http://hdl.handle.net/2445/121900
Title: | Model-driven discovery of long-chain fatty acid metabolic reprogramming in heterogeneous prostate cancer cells. |
Author: | 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 |
Keywords: | Cèl·lules canceroses Càncer de pròstata Metabolisme Epiteli Cancer cells Prostate cancer Metabolism Epithelium |
Issue Date: | 2-Jan-2018 |
Publisher: | Public Library of Science (PLoS) |
Abstract: | 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. |
Note: | Reproducció del document publicat a: https://doi.org/10.1371/journal.pcbi.1005914 |
It is part of: | PLoS Computational Biology, 2018, vol. 14, num. 1, p. e1005914 |
URI: | http://hdl.handle.net/2445/121900 |
Related resource: | https://doi.org/10.1371/journal.pcbi.1005914 |
ISSN: | 1553-734X |
Appears in Collections: | Articles publicats en revistes (Institut de Biomedicina (IBUB)) Articles publicats en revistes (Bioquímica i Biomedicina Molecular) |
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