Department of Genetic Toxicology and Cancer Biology, National Institute of Biology, Ljubljana, Slovenia.
Department of Medical Biology.
J Histochem Cytochem. 2022 Jan;70(1):29-51. doi: 10.1369/00221554211054585. Epub 2021 Oct 29.
Energy production by means of ATP synthesis in cancer cells has been investigated frequently as a potential therapeutic target in this century. Both (an)aerobic glycolysis and oxidative phosphorylation (OXPHOS) have been studied. Here, we review recent literature on energy production in glioblastoma stem cells (GSCs) and leukemic stem cells (LSCs) versus their normal counterparts, neural stem cells (NSCs) and hematopoietic stem cells (HSCs), respectively. These two cancer stem cell types were compared because their niches in glioblastoma tumors and in bone marrow are similar. In this study, it became apparent that (1) ATP is produced in NSCs and HSCs by anaerobic glycolysis, whereas fatty acid oxidation (FAO) is essential for their stem cell fate and (2) ATP is produced in GSCs and LSCs by OXPHOS despite the hypoxic conditions in their niches with FAO and amino acids providing its substrate. These metabolic processes appeared to be under tight control of cellular regulation mechanisms which are discussed in depth. However, our conclusion is that systemic therapeutic targeting of ATP production via glycolysis or OXPHOS is not an attractive option because of its unwanted side effects in cancer patients.
本世纪以来,人们频繁研究通过 ATP 合成来产生能量,以期将其作为癌症治疗的潜在靶点。人们对有氧糖酵解和氧化磷酸化(OXPHOS)都进行了研究。在这里,我们分别回顾了脑胶质瘤干细胞(GSCs)和白血病干细胞(LSCs)与正常对照细胞——神经干细胞(NSCs)和造血干细胞(HSCs)在能量产生方面的最新文献。之所以选择这两种癌症干细胞进行比较,是因为它们在脑胶质瘤肿瘤和骨髓中的龛位相似。在这项研究中,我们发现:(1)NSCs 和 HSCs 通过无氧糖酵解产生 ATP,而脂肪酸氧化(FAO)对于它们的干细胞特性至关重要;(2)GSCs 和 LSCs 通过 OXPHOS 产生 ATP,尽管它们龛位的缺氧条件下,FAO 和氨基酸为其提供底物。这些代谢过程似乎受到细胞调控机制的严格控制,我们对此进行了深入探讨。然而,我们的结论是,由于其在癌症患者中的不良副作用,通过糖酵解或 OXPHOS 进行全身性靶向治疗以抑制 ATP 产生并不是一个有吸引力的选择。