Effect of PTEN loss on metabolic reprogramming in prostate cancer cells
Effect of PTEN loss on metabolic reprogramming in prostate cancer cells
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PTEN 缺失对前列腺癌细胞代谢重编程的影响
DOI：
10.3892/ol.2019.9932
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发表时间：
2019
期刊：
影响因子：
2.9
通讯作者：
Shen Lan
中科院分区：
文献类型：
--
作者：
Zhou Xin;Yang Xu;Sun Xiang;Xu Xinyuan;Li Xi'an;Guo Yan;Wang Jiancai;Li Xia;Yao Libo;Wang He;Shen Lan
抑癌基因PTEN是前列腺癌中最常缺失的基因之一。在前列腺癌的发生发展过程中，PTEN基因的缺失是一个重要的事件。由PTEN缺失诱导的代谢重编程促进前列腺癌细胞的恶性生长和增殖。利用靶向代谢组学分析研究前列腺癌细胞中PTEN缺失对细胞内代谢途径的影响。用PTEN siRNA（siRNA-1和siRNA-2）转染DU-145细胞48小时，并通过蛋白质印迹法监测内源性PTEN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敲除的前列腺癌细胞中，大多数参与糖酵解和β-氨基丁酸解的细胞内代谢物增加。此外，大多数参与脂肪酸从头合成、脂肪酸β氧化和支链氨基酸催化剂的细胞内代谢物在PTEN敲低的前列腺癌细胞中也增加。这些结果表明，PTEN的丢失诱导前列腺癌细胞的代谢重编程，并促进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突变或缺失可通过改变糖酵解、脂肪酸代谢、支链氨基酸催化途径的代谢流，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丢失驱动的前列腺癌的贡献者之一。
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 de novo 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.