School of Medicine and Dentistry, Griffith University, Gold Coast 4222, Australia.
Faculty of Science, The University of British Columbia, Vancouver, British Columbia, Canada.
Biochim Biophys Acta Mol Basis Dis. 2024 Jun;1870(5):167164. doi: 10.1016/j.bbadis.2024.167164. Epub 2024 Apr 9.
Cancer stem cells (CSCs) are a subset of tumor cells that can initiate and sustain tumor growth and cause recurrence and metastasis. CSCs are particularly resistant to conventional therapies compared to their counterparts, owing greatly to their intrinsic metabolic plasticity. Metabolic plasticity allows CSCs to switch between different energy production and usage pathways based on environmental and extrinsic factors, including conditions imposed by conventional cancer therapies. To cope with nutrient deprivation and therapeutic stress, CSCs can transpose between glycolysis and oxidative phosphorylation (OXPHOS) metabolism. The mechanism behind the metabolic pathway switch in CSCs is not fully understood, however, some evidence suggests that the tumor microenvironment (TME) may play an influential role mediated by its release of signals, such as Wnt/β-catenin and Notch pathways, as well as a background of hypoxia. Exploring the factors that promote metabolic plasticity in CSCs offers the possibility of eventually developing therapies that may more effectively eliminate the crucial tumor cell subtype and alter the disease course substantially.
癌症干细胞（CSCs）是肿瘤细胞的一个亚群，能够启动和维持肿瘤生长，并导致复发和转移。与普通肿瘤细胞相比，CSCs 对传统疗法具有更强的抵抗力，这主要归因于其内在的代谢可塑性。代谢可塑性使 CSCs 能够根据环境和外在因素（包括传统癌症疗法施加的条件）在不同的能量产生和使用途径之间切换。为了应对营养缺乏和治疗压力，CSCs 可以在糖酵解和氧化磷酸化（OXPHOS）代谢之间转换。然而，CSCs 中代谢途径转换的机制尚不完全清楚，一些证据表明肿瘤微环境（TME）可能通过其释放的信号（如 Wnt/β-catenin 和 Notch 途径）以及缺氧背景发挥影响作用。探索促进 CSCs 代谢可塑性的因素为最终开发可能更有效地消除关键肿瘤细胞亚型并显著改变疾病进程的治疗方法提供了可能性。
