Model-driven discovery of long-chain fatty acid metabolic reprogramming in heterogeneous prostate cancer cells

• DOI: 10.1371/journal.pcbi.1005914
• Publication Date: 2018-01-02T19:10:29Z
• Authors: Igor Marín de Mas; Esther Aguilar; Erika Zodda; Cristina Balcells; Silvia Marin; Guido Dallmann; Timothy M. Thomson; Balázs Papp; Marta Cascante
• Keywords: Eicosanoid metabolism; Reprogramming

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 line (PC-3) into genome-scale metabolic network model to explore their differences potential vulnerabilities. In this dual model, PC-3/S cells express markers display high low metastatic potential, while PC-3/M present the opposite phenotype higher proliferative rate. Model-driven analysis experimental validations unveiled marked reprogramming in long-chain fatty acids metabolism. While showed an enhanced entry of mitochondria, used as precursors eicosanoid suggest that endows with augmented energy metabolism fast proliferation increased production impacting angiogenesis, adhesion invasion. also accumulation docosahexaenoic acid, acid antiproliferative effects. The therapeutic significance our was supported differential sensitivity etomoxir, inhibitor transport mitochondria.