Reconstruction of tissue-specific genome-scale metabolic models for human cancer stem cells. (March 2022)

• Record Type: Journal Article
• Authors: Barata, Tânia; Vieira, Vítor; Rodrigues, Rúben; Neves, Ricardo Pires das; Rocha, Miguel
• Is Part Of: Computers in biology and medicine. Volume 142(2022)
• Publication Date: 2022-03
• Subjects: Cancer Stem Cells (CSCs) -- Genome-Scale Metabolic Models (GSMMs) -- miRNAs -- Antimetabolites -- Transcription Factors (TFs); Medicine -- Data processing -- Periodicals; Biology -- Data processing -- Periodicals; 610.285
• DOI: 10.1016/j.compbiomed.2021.105177
• Languages: English
• ISSNs: 0010-4825

Abstract

Abstract: 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. Highlights: Metabolism of cancer stem cells promotes cancer aggressiveness and maintenance. Tissue-specific genome-scale metabolic models were built for cancer stem cells. Predicted metabolic properties were in accordance with those reported in literature. New potential targets and compounds were identified.