Zhou Xin, Yang Xu, Sun Xiang, Xu Xinyuan, Li Xi'an, Guo Yan, Wang Jiancai, Li Xia, Yao Libo, Wang He, Shen Lan
The State Key Laboratory of Cancer Biology, Department of Biochemistry and Molecular Biology, The Fourth Military Medical University, Xi'an, Shaanxi 710032, P.R. China.
Department of Urology, Tangdu Hospital, The Fourth Military Medical University, Xi'an, Shaanxi 710032, P.R. China.
Oncol Lett. 2019 Mar;17(3):2856-2866. doi: 10.3892/ol.2019.9932. Epub 2019 Jan 14.
The tumor suppressor gene PTEN is one of the most often deleted genes in human prostate cancer. Loss of PTEN is an important event in prostate carcinogenesis. Metabolic reprogramming induced by PTEN loss fuels malignant growth and proliferation of prostate cancer cells. Targeted metabolomics analysis was used to investigate the effects of PTEN loss on intracellular metabolic pathways in prostate cancer cells. DU-145 cells were transfected with PTEN siRNAs (siRNA-1 and siRNA-2) for 48 h, and endogenous PTEN expression was monitored by western blotting. Changes in intracellular metabolites were determined by liquid chromatography-tandem mass chromatography (LC-MS/MS) and gas chromatography-mass spectrometry (GC-MS). Most intracellular metabolites involved in glycolysis and glutaminolysis were increased in PTEN knockdown prostate cancer cells. In addition, most intracellular metabolites involved in fatty acid synthesis, fatty acid beta oxidation and branched chain amino acid catabolism were also increased in PTEN knockdown prostate cancer cells. These results revealed that PTEN loss induced the metabolic reprogramming of prostate cancer cells and promoted the malignant proliferation of prostate cancer cells. The present metabolomics analysis indicates that tumor suppressor gene PTEN mutation or deletion can induce metabolic reprogramming in prostate cancer cells and tumorigenesis by altering the metabolic flux of glycolysis, glutaminolysis, fatty acid metabolism and branched chain amino acid catabolism pathways. Metabolic reprogramming is one of the contributors to PTEN-loss driven prostate cancer.
肿瘤抑制基因PTEN是人类前列腺癌中最常缺失的基因之一。PTEN的缺失是前列腺癌发生过程中的一个重要事件。PTEN缺失诱导的代谢重编程为前列腺癌细胞的恶性生长和增殖提供了动力。采用靶向代谢组学分析来研究PTEN缺失对前列腺癌细胞内代谢途径的影响。将DU-145细胞用PTEN siRNA（siRNA-1和siRNA-2）转染48小时，通过蛋白质免疫印迹法监测内源性PTEN的表达。通过液相色谱-串联质谱（LC-MS/MS）和气相色谱-质谱（GC-MS）测定细胞内代谢物的变化。在PTEN敲低的前列腺癌细胞中，大多数参与糖酵解和谷氨酰胺分解的细胞内代谢物增加。此外，在PTEN敲低的前列腺癌细胞中，大多数参与脂肪酸合成、脂肪酸β氧化和支链氨基酸分解代谢的细胞内代谢物也增加。这些结果表明，PTEN缺失诱导了前列腺癌细胞的代谢重编程，并促进了前列腺癌细胞的恶性增殖。目前的代谢组学分析表明，肿瘤抑制基因PTEN的突变或缺失可通过改变糖酵解、谷氨酰胺分解、脂肪酸代谢和支链氨基酸分解代谢途径的代谢通量，诱导前列腺癌细胞的代谢重编程和肿瘤发生。代谢重编程是PTEN缺失驱动的前列腺癌的促成因素之一。
