Cancer Metabolism Group, Department of Oncology, Luxembourg Institute of Health, L-1526 Luxembourg, Luxembourg.
Faculty of Science, Technology and Medicine, University of Luxembourg, 2 Avenue de l'Université, L-4365 Esch-sur-Alzette, Luxembourg.
Cells. 2020 Sep 5;9(9):2035. doi: 10.3390/cells9092035.
The metastatic cascade is a highly plastic and dynamic process dominated by cellular heterogeneity and varying metabolic requirements. During this cascade, the three major metabolic pillars, namely biosynthesis, RedOx balance, and bioenergetics, have variable importance. Biosynthesis has superior significance during the proliferation-dominated steps of primary tumour growth and secondary macrometastasis formation and only minor relevance during the growth-independent processes of invasion and dissemination. Consequently, RedOx homeostasis and bioenergetics emerge as conceivable metabolic key determinants in cancer cells that disseminate from the primary tumour. Within this review, we summarise our current understanding on how cancer cells adjust their metabolism in the context of different microenvironments along the metastatic cascade. With the example of one-carbon metabolism, we establish a conceptual view on how the same metabolic pathway can be exploited in different ways depending on the current cellular needs during metastatic progression.
转移级联是一个高度可塑性和动态的过程,主要由细胞异质性和不同的代谢需求决定。在这个级联过程中,三大主要代谢支柱,即生物合成、RedOx 平衡和生物能量学,具有不同的重要性。在原发性肿瘤生长和继发性巨转移形成的增殖主导阶段,生物合成具有更高的意义,而在侵袭和扩散等独立于生长的过程中则相关性较小。因此,RedOx 平衡和生物能量学成为癌症细胞从原发性肿瘤扩散时可以想象的代谢关键决定因素。在这篇综述中,我们总结了我们目前对癌细胞如何在转移级联过程中不同微环境下调整代谢的理解。以一碳代谢为例,我们建立了一个概念性的观点,即同一种代谢途径可以根据转移进展过程中当前的细胞需求以不同的方式被利用。