Key Laboratory of Biorheological Science & Technology, Ministry of Education, College of Bioengineering, Chongqing University, Chongqing 400030, China.
Department of Mechanical Science and Engineering, Nagoya University, Nagoya 464-8603, Japan.
Int J Mol Sci. 2020 Jul 25;21(15):5276. doi: 10.3390/ijms21155276.
Cancer stem cells (CSCs) are considered to be the main cause of tumor recurrence, metastasis, and an unfavorable prognosis. Energy metabolism is closely associated with cell stemness. However, how the stemness of liver cancer stem cells (LCSCs) is regulated by metabolic/oxidative stress remains poorly understood. In this study, we compare the metabolic differences between LCSCs and the hepatocellular carcinoma cell line HCCLM3, and explore the relationship between metabolism and LCSC stemness. We found that LCSCs from the hepatocellular carcinoma cell HCCLM3 exhibited more robust glucose metabolism than HCCLM3, including glycolysis, oxidative phosphorylation (OXPHOS), and pyruvate produced by glycolysis entering mitochondria for OXPHOS. Moreover, 2-deoxy-D-glucose (2-DG) enhanced the LCSC stemness by upregulating OXPHOS. In contrast, Mdivi-1 reduced the levels of OXPHOS and weakened the stemness by inhibiting mitochondrial fission. Together, our findings clarify the relationship between energy metabolism and LCSC stemness and may provide theoretical guidance and potential therapeutic approaches for liver cancer.
癌症干细胞（CSCs）被认为是肿瘤复发、转移和预后不良的主要原因。能量代谢与细胞干性密切相关。然而，肝癌干细胞（LCSCs）的干性如何受到代谢/氧化应激的调节仍知之甚少。在这项研究中，我们比较了 LCSCs 和肝癌细胞系 HCCLM3 之间的代谢差异，并探讨了代谢与 LCSC 干性之间的关系。我们发现，来自肝癌细胞 HCCLM3 的 LCSCs比 HCCLM3 具有更强的葡萄糖代谢能力，包括糖酵解、氧化磷酸化（OXPHOS）以及糖酵解产生的丙酮酸进入线粒体进行 OXPHOS。此外，2-脱氧-D-葡萄糖（2-DG）通过上调 OXPHOS 增强了 LCSC 干性。相反，Mdivi-1 通过抑制线粒体分裂降低了 OXPHOS 水平并减弱了干性。总之，我们的研究结果阐明了能量代谢与 LCSC 干性之间的关系，并可能为肝癌提供理论指导和潜在的治疗方法。
