Reconstruction of tissue-specific genome-scale metabolic models for human cancer stem cells.

Autor: Barata T; CNC - Center for Neuroscience and Cell Biology, CIBB - Centre for Innovative Biomedicine and Biotechnology, University of Coimbra, 3004-517, Coimbra, Portugal., Vieira V; Centre of Biological Engineering, University of Minho - Campus de Gualtar, Braga, Portugal., Rodrigues R; Centre of Biological Engineering, University of Minho - Campus de Gualtar, Braga, Portugal., Neves RPD; CNC - Center for Neuroscience and Cell Biology, CIBB - Centre for Innovative Biomedicine and Biotechnology, University of Coimbra, 3004-517, Coimbra, Portugal; IIIUC-Institute of Interdisciplinary Research, University of Coimbra, 3030-789, Coimbra, Portugal. Electronic address: ricardo.neves@uc-biotech.pt., Rocha M; Centre of Biological Engineering, University of Minho - Campus de Gualtar, Braga, Portugal; Department of Informatics, University of Minho. Electronic address: mrocha@di.uminho.pt.
Jazyk: angličtina
Zdroj: Computers in biology and medicine [Comput Biol Med] 2022 Mar; Vol. 142, pp. 105177. Date of Electronic Publication: 2021 Dec 29.
DOI: 10.1016/j.compbiomed.2021.105177
Abstrakt: Cancer Stem Cells (CSCs) contribute to cancer aggressiveness, metastasis, chemo/radio-therapy resistance, and tumor recurrence. Recent studies emphasized the importance of metabolic reprogramming of CSCs for the maintenance and progression of the cancer phenotype through both the fulfillment of the energetic requirements and the supply of substrates fundamental for fast-cell growth, as well as through metabolite-induced epigenetic regulation. Therefore, it is of paramount importance to develop therapeutic strategies tailored to target the metabolism of CSCs. In this work, we built computational Genome-Scale Metabolic Models (GSMMs) for CSCs of different tissues. Flux simulations were then used to predict metabolic phenotypes, identify potential therapeutic targets, and spot already-known Transcription Factors (TFs), miRNAs and antimetabolites that could be used as part of drug repurposing strategies against cancer. Results were in accordance with experimental evidence, provided insights of new metabolic mechanisms for already known agents, and allowed for the identification of potential new targets and compounds that could be interesting for further in vitro and in vivo validation.
(Copyright © 2021 Elsevier Ltd. All rights reserved.)
Databáze: MEDLINE
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