The Catholic University Liver Research Center &WHO Collaborating Center of Viral Hepatitis, College of Medicine, The Catholic University of Korea, Seoul 06591, Republic of Korea.
Metabolic and Biomolecular Engineering National Research Laboratory, Department of Chemical and Biomolecular Engineering (BK21 Plus program), Center for Systems and Synthetic Biotechnology, Institute for the BioCentury, Korea Advanced Institute of Science and Technology (KAIST), Daejeon 34141, Republic of Korea.
Sci Rep. 2017 Apr 3;7:45557. doi: 10.1038/srep45557.
Liver cancer stem cells (LCSCs) have attracted attention because they cause therapeutic resistance in hepatocellular carcinoma (HCC). Understanding the metabolism of LCSCs can be a key to developing therapeutic strategy, but metabolic characteristics have not yet been studied. Here, we systematically analyzed and compared the global metabolic phenotype between LCSCs and non-LCSCs using transcriptome and metabolome data. We also reconstructed genome-scale metabolic models (GEMs) for LCSC and non-LCSC to comparatively examine differences in their metabolism at genome-scale. We demonstrated that LCSCs exhibited an increased proliferation rate through enhancing glycolysis compared with non-LCSCs. We also confirmed that MYC, a central point of regulation in cancer metabolism, was significantly up-regulated in LCSCs compared with non-LCSCs. Moreover, LCSCs tend to have less active fatty acid oxidation. In this study, the metabolic characteristics of LCSCs were identified using integrative systems analysis, and these characteristics could be potential cures for the resistance of liver cancer cells to anticancer treatments.
肝癌干细胞（LCSCs）因其在肝细胞癌（HCC）中引起治疗抵抗而引起关注。了解 LCSCs 的代谢可能是开发治疗策略的关键，但代谢特征尚未得到研究。在这里，我们使用转录组和代谢组数据系统地分析和比较了 LCSCs 和非 LCSCs 之间的全局代谢表型。我们还为 LCSC 和非 LCSC 重建了基因组规模的代谢模型（GEM），以比较基因组规模的代谢差异。我们证明 LCSCs 通过增强糖酵解与非 LCSCs 相比表现出更高的增殖率。我们还证实，与非 LCSCs 相比，癌代谢调控的中心点 MYC 在 LCSCs 中显著上调。此外，LCSCs 往往具有较少的活跃脂肪酸氧化。在这项研究中，通过整合系统分析确定了 LCSCs 的代谢特征，这些特征可能是治疗肝癌细胞对抗癌治疗产生耐药性的潜在方法。
