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DC Field | Value | Language |
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dc.contributor.author | Marín de Mas, Igor Bartolomé | - |
dc.contributor.author | Aguilar Fadó, Esther | - |
dc.contributor.author | Zodda, Erika | - |
dc.contributor.author | Balcells Nadal, Cristina | - |
dc.contributor.author | Marín Martínez, Silvia | - |
dc.contributor.author | Dallmann, Guido | - |
dc.contributor.author | Thomson, Timothy M. | - |
dc.contributor.author | Papp, Balázs | - |
dc.contributor.author | Cascante i Serratosa, Marta | - |
dc.date.accessioned | 2018-04-26T10:34:16Z | - |
dc.date.available | 2018-04-26T10:34:16Z | - |
dc.date.issued | 2018-01-02 | - |
dc.identifier.issn | 1553-734X | - |
dc.identifier.uri | http://hdl.handle.net/2445/121900 | - |
dc.description.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. | - |
dc.format.extent | 20 p. | - |
dc.format.mimetype | application/pdf | - |
dc.language.iso | eng | - |
dc.publisher | Public Library of Science (PLoS) | - |
dc.relation.isformatof | Reproducció del document publicat a: https://doi.org/10.1371/journal.pcbi.1005914 | - |
dc.relation.ispartof | PLoS Computational Biology, 2018, vol. 14, num. 1, p. e1005914 | - |
dc.relation.uri | https://doi.org/10.1371/journal.pcbi.1005914 | - |
dc.rights | cc-by (c) Marin-de Mas, Igor et al., 2018 | - |
dc.rights.uri | http://creativecommons.org/licenses/by/3.0/es | - |
dc.source | Articles publicats en revistes (Bioquímica i Biomedicina Molecular) | - |
dc.subject.classification | Cèl·lules canceroses | - |
dc.subject.classification | Càncer de pròstata | - |
dc.subject.classification | Metabolisme | - |
dc.subject.classification | Epiteli | - |
dc.subject.other | Cancer cells | - |
dc.subject.other | Prostate cancer | - |
dc.subject.other | Metabolism | - |
dc.subject.other | Epithelium | - |
dc.title | Model-driven discovery of long-chain fatty acid metabolic reprogramming in heterogeneous prostate cancer cells. | - |
dc.type | info:eu-repo/semantics/article | - |
dc.type | info:eu-repo/semantics/publishedVersion | - |
dc.identifier.idgrec | 679073 | - |
dc.date.updated | 2018-04-26T10:34:16Z | - |
dc.relation.projectID | info:eu-repo/grantAgreement/EC/FP7/264780/EU//METAFLUX | - |
dc.rights.accessRights | info:eu-repo/semantics/openAccess | - |
dc.identifier.pmid | 29293497 | - |
Appears in Collections: | Articles publicats en revistes (Institut de Biomedicina (IBUB)) Articles publicats en revistes (Bioquímica i Biomedicina Molecular) |
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679073.pdf | 4.69 MB | Adobe PDF | View/Open |
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