Glucose transporters in cancer metabolism.
Glucose transporters in cancer metabolism.
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癌代谢中的葡萄糖转运蛋白。
DOI：
10.1097/cco.0b013e328356da72
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发表时间：
2012-11
影响因子：
3.4
通讯作者：
Shanmugam M
中科院分区：
文献类型：
--
作者：
Adekola K;Rosen ST;Shanmugam M
转化细胞的葡萄糖消耗率高于ATP合成所需的葡萄糖消耗率。葡萄糖有助于生物量的产生，并调节对致癌进程至关重要的细胞信号。葡萄糖利用中一个关键的速率限制步骤是葡萄糖跨质膜的运输。这篇综述将重点介绍关键的葡萄糖转运蛋白(GLUT)和目前针对这类蛋白的治疗方法。谷氨酸能够促进葡萄糖进入细胞，越来越多的人发现，在癌症中，谷氨酸被解除了调控。尽管GLUT的癌症特异性表达模式正在被确定，但仍需要全面的分析来证实单个GUT的作用。将GLUT定义为在特定肿瘤环境中具有限速作用的研究，通过人工致死性筛选鉴定GLUT1抑制剂，在骨髓瘤中新的参与胰岛素反应的GLUT4，以及鉴定GLUT9是尿酸盐转运体，这些都是关键的进展，突显了对这一大而神秘的蛋白质类别继续研究的必要性。肿瘤细胞表现出高水平的葡萄糖摄取，这一现象已被用于使用放射性标记葡萄糖类似物对广泛的癌症进行预后和诊断成像。然而，我们还不能以肿瘤细胞特异性的方式靶向葡萄糖进入进行治疗。谷氨酰胺已被证实在特定的肿瘤环境中具有限速作用。肿瘤特异性GLUT的识别和靶向为更全面地阻断葡萄糖调节的代谢和信号转导提供了一种很有前途的方法。
Transformed cells exhibit a high rate of glucose consumption beyond that necessary for ATP synthesis. Glucose aids in the generation of biomass and regulates cellular signaling critical for oncogenic progression. A key rate-limiting step in glucose utilization is the transport of glucose across the plasma membrane. This review will highlight key glucose transporters (GLUTs) and current therapies targeting this class of proteins. GLUTs, enabling the facilitative entry of glucose into a cell, are increasingly found to be deregulated in cancer. Although cancer-specific expression patterns for GLUTs are being identified, comprehensive analyses substantiating a role for individual GLUTs are still required. Studies defining GLUTs as being rate-limiting in specific tumor contexts, the identification of GLUT1 inhibitors via synthetic lethality screens, novel engagement of the insulin-responsive GLUT4 in myeloma and identification of GLUT9 being a urate transporter, are key advances underscoring the need for continued investigation of this large and enigmatic class of proteins. Tumor cells exhibit elevated levels of glucose uptake, a phenomenon that has been capitalized upon for the prognostic and diagnostic imaging of a wide range of cancers using radio-labeled glucose analogs. We have, however, not yet been able to target glucose entry in a tumor cell-specific manner for therapy. GLUTs have been identified as rate-limiting in specific tumor contexts. The identification and targeting of tumor-specific GLUTs provide a promising approach to block glucose-regulated metabolism and signaling more comprehensively.