Genome-Scale Tissue-specific Reconstruction and Analysis of Metabolic Network in Glioblastoma multiform and Glioblastoma Stem Cells for Identification of Novel Anti-Brain Tumor Drug Targets

Cancer stem cells (CSCs) are a subpopulation of tumor tissue with the ability to generate tumor cells through the process of self-renewal and differentiation to other cell types. Growing evidence suggests that cancer can be regarded as a metabolic disease and the stem-like behavior of CSCs are also highly controlled by metabolic mechanisms. Given the complexity of metabolism, a comprehensive understanding of metabolic mechanisms underlying tumorigenesis requires a systems approach. Genome-scale constraint-based metabolic models are currently the most advanced tools for quantitative characterization of metabolism. In the present study, we took a constraint-based metabolic reconstruction and analysis (COBRA) approach to develop in silico genome-scale models of glioblastoma multiform (GBM) and its stem cells to enable structural and functional characterization of metabolism in these cells. Our holistic analysis of the metabolic network reflected the current knowledge of GBM and led to identification of novel anti-tumor targets and promising drug repositioning scenarios for synergistic treatment of brain tumor malignancy.

کلیدواژه ها:

Glioblastoma multiform ، Systems biology ، Genome-scale modeling ، Constrain-based analysis ، Metabolic network ، Metabolic reconstruction