Decreased glucose bioavailability and elevated aspartate metabolism in prostate cancer cells undergoing epithelial-mesenchymal transition
Decreased glucose bioavailability and elevated aspartate metabolism in prostate cancer cells undergoing epithelial-mesenchymal transition
复制标题
经历上皮间质转化的前列腺癌细胞中葡萄糖生物利用度降低和天冬氨酸代谢升高
DOI：
10.1002/jcp.29490
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发表时间：
2020-02-04
影响因子：
5.6
通讯作者：
Li, Lei
中科院分区：
文献类型：
--
作者：
Chen, Yule;Wang, Ke;Li, Lei
前列腺癌（PCa）是一种常见的恶性肿瘤，具有高度的转移倾向。上皮 - 间质转化（EMT）在前列腺癌转移中起着至关重要的作用。代谢重编程为癌症发展提供了代谢优势，并可能导致发现癌症治疗的新靶点。然而，经历上皮 - 间质转化的前列腺癌细胞的代谢特征仍不清楚。我们利用代谢组学和转录组学分析发现，经历上皮 - 间质转化的前列腺癌细胞葡萄糖利用受损。体外研究表明，经历上皮 - 间质转化的前列腺癌细胞对葡萄糖的依赖程度低于上皮样前列腺癌细胞。然而，经历上皮 - 间质转化的细胞天冬氨酸及其下游代谢产物水平较高，这表明天冬氨酸代谢上调。由于天冬氨酸是人类癌细胞上皮 - 间质转化和转移的一个促成因素，我们得出结论，这种代谢重编程可能在上皮 - 间质转化和前列腺癌进展中起着至关重要的作用。
Prostate cancer (PCa) is a common malignancy with a high tendency for metastasis. Epithelial-mesenchymal transition (EMT) plays a crucial role in PCa metastasis. Metabolic reprogramming offers metabolic advantages for cancer development and could result in the discovery of novel targets for cancer therapy. However, the metabolic features of PCa cells undergoing EMT remain unclear. We used metabolome and transcriptome analyses and found that PCa cells undergoing EMT showed impaired glucose utilization. In vitro studies demonstrated that PCa cells undergoing EMT were less addicted to glucose than epithelial-like PCa cells. However, cells that underwent EMT had higher levels of aspartate and its downstream metabolites, indicative of upregulated aspartate metabolism. As aspartate is a contributor for EMT and metastasis in human cancer cells, we conclude that this metabolic reprogramming may play a vital role in EMT and PCa progression.