Cancer Signalling and Metabolism Group, Instituto de Investigação e Inovação em Saúde (I3S), Universidade do Porto, 4200-135 Porto, Portugal.
Cancer Signalling and Metabolism Group, Institute of Molecular Pathology and Immunology of the University of Porto (Ipatimup), 4200-465 Porto, Portugal.
Dis Model Mech. 2018 Jun 28;11(8):dmm033464. doi: 10.1242/dmm.033464.
Cancer stem cells are a subpopulation of cells within a tumour believed to confer resistance to standard cancer therapies. Although many studies have addressed the specific mechanisms of tumour recurrence driven by cancer stem cells, cellular metabolism is an often-neglected attribute. The metabolic features of cancer stem cells are still poorly understood, and they thus constitute a promising field in cancer research. The findings published so far point to a distinct metabolic phenotype in cancer stem cells, which might depend on the cancer type, the model system used or even the experimental design, and several controversies still need to be tackled. This Review describes the metabolic phenotype of cancer stem cells by addressing the main metabolic traits in different tumours, including glycolysis and oxidative, glutamine, fatty acid and amino acid metabolism. In the context of these pathways, we also mention the specific alterations in metabolic enzymes and metabolite levels that have a role in the regulation of cancer stemness. Determining the role of metabolism in supporting resistance to therapy driven by cancer stem cells can raise the opportunity for novel therapeutic targets, which might not only eliminate this resistant population, but, more importantly, eradicate the whole tumour in a relapse-free scenario.
肿瘤干细胞是肿瘤细胞中的一个亚群,被认为能够赋予肿瘤对标准癌症治疗的抗性。尽管许多研究已经解决了由肿瘤干细胞驱动的肿瘤复发的特定机制,但细胞代谢是一个经常被忽视的属性。肿瘤干细胞的代谢特征仍未被充分理解,因此它们构成了癌症研究中一个有前途的领域。迄今为止发表的研究结果表明,肿瘤干细胞具有独特的代谢表型,这可能取决于癌症类型、使用的模型系统甚至实验设计,并且仍需要解决几个争议。本综述通过研究不同肿瘤中的主要代谢特征,包括糖酵解和氧化、谷氨酰胺、脂肪酸和氨基酸代谢,描述了肿瘤干细胞的代谢表型。在这些途径的背景下,我们还提到了代谢酶和代谢物水平的特定改变,这些改变在调节肿瘤干细胞特性中起作用。确定代谢在支持肿瘤干细胞驱动的治疗耐药中的作用,可以为新的治疗靶点提供机会,这不仅可以消除这种耐药群体,而且更重要的是,可以在无复发的情况下根除整个肿瘤。