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在经历上皮-间质转化的前列腺癌细胞中,葡萄糖生物利用度降低,天冬氨酸代谢升高。

Decreased glucose bioavailability and elevated aspartate metabolism in prostate cancer cells undergoing epithelial-mesenchymal transition.

机构信息

Department of Urology, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, P.R. China.

Oncology Research Laboratory, Key Laboratory of Environment and Genes Related to Diseases, Ministry of Education, Xi'an, P.R. China.

出版信息

J Cell Physiol. 2020 Jul;235(7-8):5602-5612. doi: 10.1002/jcp.29490. Epub 2020 Feb 4.

DOI:10.1002/jcp.29490
PMID:32017073
Abstract

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.

摘要

前列腺癌(PCa)是一种常见的恶性肿瘤,具有很高的转移倾向。上皮-间充质转化(EMT)在 PCa 转移中起着关键作用。代谢重编程为癌症的发展提供了代谢优势,并可能为癌症治疗发现新的靶点。然而,发生 EMT 的 PCa 细胞的代谢特征尚不清楚。我们使用代谢组学和转录组学分析发现,发生 EMT 的 PCa 细胞表现出葡萄糖利用受损。体外研究表明,发生 EMT 的 PCa 细胞比上皮样 PCa 细胞对葡萄糖的依赖性更低。然而,发生 EMT 的细胞中天冬氨酸及其下游代谢物水平更高,表明天冬氨酸代谢上调。由于天冬氨酸是人类癌细胞 EMT 和转移的贡献者,我们得出结论,这种代谢重编程可能在 EMT 和 PCa 进展中发挥重要作用。

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