PTEN-deficient cells prefer glutamine for metabolic synthesis

PTEN-deficient cells prefer glutamine for metabolic synthesis
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PTEN 缺陷细胞更喜欢谷氨酰胺进行代谢合成

DOI:
10.1093/abbs/gmz163
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发表时间:
2020-03
影响因子:
3.7
通讯作者:
Hua Xiangdong
Hua Xiangdong
中科院分区:
生物学3区
文献类型:
--
作者:
Wang Zhichao;Chen Di;Piao Hai-Long;Hua Xiangdong

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PTEN loss-of-function mutations frequently occur in gliomas and lead to poor overall survival. PTEN deficiency induces metabolic reprogramming, which may provide therapeutic targets. PTEN is known to impact the Warburg effect and glutaminolysis. To uncover essential glutamine-related metabolic changes specific in PTEN-deficient cells and thus provide potential therapeutic targets, we performed capillary electrophoresis–mass spectrometry-based metabolomics analysis and metabolic flux analysis under different glutamine culture conditions and PTEN alteration status. Glu, Asn, Gly, Ala, and 1-methylnicotinamide were decreased in PTEN-deficient cells under normal culture conditions. Meanwhile, under Gln-deprived culture conditions, Glu, citrate, and UTP synthesis were reduced and acetyl carnitine was increased in PTEN-deficient cells. The reliance on Gln was increased for metabolic intermediates synthesis but decreased for energy production in PTEN-deficient cells. However, the reliance on Gln for UTP synthesis cannot be targeted due to anaplerotic synthesis of UTP from other sources. How to target these metabolic addictions needs further research.
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