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2018-01-02

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cc-by (c) Marin-de Mas, Igor et al., 2018
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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Recurs relacionat

https://doi.org/10.1371/journal.pcbi.1005914

Resum

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.

Matèries

Cèl·lules canceroses, Càncer de pròstata, Metabolisme, Epiteli

Matèries (anglès)

Cancer cells, Prostate cancer, Metabolism, Epithelium

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Articles publicats en revistes (Bioquímica i Biomedicina Molecular)
Articles publicats en revistes (Institut de Biomedicina (IBUB))

Citació

MARÍN DE MAS, Igor Bartolomé, et al. 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. ISSN 1553-734X. [consulta: 8 de maig de 2026]. Disponible a: https://hdl.handle.net/2445/121900

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