GLUT3 induced by AMPK/CREB1 axis is key for withstanding energy stress and augments the efficacy of current colorectal cancer therapies
GLUT3 induced by AMPK/CREB1 axis is key for withstanding energy stress and augments the efficacy of current colorectal cancer therapies
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AMPK/CREB1 轴诱导的 GLUT3 是抵抗能量应激并增强当前结直肠癌治疗功效的关键。
DOI：
10.1038/s41392-020-00220-9
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发表时间：
2020-09-02
影响因子：
39.3
通讯作者：
Cai, Guoxiang
中科院分区：
文献类型：
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作者：
Dai, Weixing;Xu, Ye;Cai, Guoxiang
癌细胞通常以葡萄糖代谢过度活跃为特征，这往往会导致葡萄糖缺乏；因此，需要重新连接癌症代谢的替代途径。在这里，我们证明 GLUT3 在结直肠癌 (CRC) 中高表达，并且与 CRC 患者的预后呈负相关，而 GLUT1 与 CRC 预后无关。在葡萄糖限制条件下，GLUT3 通过加速葡萄糖输入和促进核苷酸合成来加速 CRC 细胞的生长。值得注意的是，在葡萄糖限制应激下，GLUT3 对细胞生长的影响比 GLUT1 更大。从机制上讲，低血糖应激通过 AMPK/CREB1 途径显着上调 GLUT3。此外，高 GLUT3 表达显着增加了 CRC 细胞对维生素 C 和含维生素 C 方案治疗的敏感性。总之，这项研究的结果强调了 AMPK/CREB1/GLUT3 通路对于 CRC 细胞承受葡萄糖限制应激的重要性，并强调了维生素 C 在高 GLUT3 表达的 CRC 中的治疗潜力。
Cancer cells are usually characterized by hyperactive glucose metabolism, which can often lead to glucose scarcity; thus, alternative pathways to rewire cancer metabolism are required. Here, we demonstrated that GLUT3 was highly expressed in colorectal cancer (CRC) and negatively linked to CRC patient outcomes, whereas GLUT1 was not associated with CRC prognosis. Under glucose-limiting conditions, GLUT3 expedited CRC cell growth by accelerating glucose input and fuelling nucleotide synthesis. Notably, GLUT3 had a greater impact on cell growth than GLUT1 under glucose-limiting stress. Mechanistically, low-glucose stress dramatically upregulated GLUT3 via the AMPK/CREB1 pathway. Furthermore, high GLUT3 expression remarkably increased the sensitivity of CRC cells to treatment with vitamin C and vitamin C-containing regimens. Together, the results of this study highlight the importance of the AMPK/CREB1/GLUT3 pathway for CRC cells to withstand glucose-limiting stress and underscore the therapeutic potential of vitamin C in CRC with high GLUT3 expression.