Swiss Institute for Experimental Cancer Research, School of Life Sciences, Ecole Polytechnique Fédérale de Lausanne, Switzerland.
FEBS J. 2018 Aug;285(16):2926-2943. doi: 10.1111/febs.14577. Epub 2018 Jun 25.
Solute carriers of the glucose transporter (GLUT) family mediate the first step for cellular glucose usage. The upregulation of GLUTs has been reported in numerous cancer types as a result of perturbation of gene expression or protein relocalization or stabilization. Because they enable to sustain the energy demand required by tumor cells for various biochemical programs, they are promising targets for the development of anticancer strategies. Recently, important biological insights have come from the fine crystal structure determination of several GLUTs; these advances will likely catalyze the development of new selective inhibitory compounds. Furthermore, deregulated glucose metabolism of nontumor cells in the tumor mass is beginning to be appreciated and could have major implications for our understanding of how glucose uptake by specific cell types influences the behavior of neighboring cells in the same microenvironment. In this review, we discuss some of the deregulation mechanisms of glucose transporters, their genetic and pharmacological targeting in cancer, and new functions they may have in nontumor cells of the tumor environment or beyond glucose uptake for glycolysis.
葡萄糖转运体（GLUT）家族的溶质载体介导细胞葡萄糖利用的第一步。由于基因表达或蛋白质重定位或稳定化的干扰，许多癌症类型中都报道了 GLUT 的上调。因为它们能够维持肿瘤细胞进行各种生化程序所需的能量需求，所以它们是开发抗癌策略的有前途的靶标。最近，从几个 GLUT 的精细晶体结构测定中获得了重要的生物学见解；这些进展可能会促进新的选择性抑制化合物的开发。此外，肿瘤中肿瘤细胞外的葡萄糖代谢失调开始受到重视，这可能对我们理解特定细胞类型摄取葡萄糖如何影响同一微环境中相邻细胞的行为产生重大影响。在这篇综述中，我们讨论了葡萄糖转运体的一些失调机制，它们在癌症中的遗传和药理学靶向，以及它们在肿瘤环境中的非肿瘤细胞或糖酵解以外的葡萄糖摄取中可能具有的新功能。
