UGCG influences glutamine metabolism of breast cancer cells
UGCG influences glutamine metabolism of breast cancer cells
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DOI：
10.1038/s41598-019-52169-7
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发表时间：
2019-10-30
影响因子：
4.6
通讯作者：
Wegner, Marthe-Susanna
中科院分区：
文献类型：
--
作者：
Schoemel, Nina;Hancock, Sarah E.;Wegner, Marthe-Susanna
UDP-葡萄糖神经酰胺葡萄糖基转移酶（UGCG）是鞘糖脂（GSL）代谢的关键酶，是唯一能从头产生葡萄糖神经酰胺（GlcCer）的酶。UGCG合成增加与促癌过程相关，例如几种癌症类型中的增殖增加和多药耐药性。我们研究了UGCG过表达对乳腺癌细胞谷氨酰胺代谢的影响。我们观察到适应葡萄糖和谷氨酰胺摄取在有限的能量供应环境下UGCG过表达。谷氨酰胺用于增强氧化应激反应，表现为谷氨酰胺代谢蛋白如谷胱甘肽-二硫键还原酶（GSR）的mRNA表达增加，导致还原型谷胱甘肽（GSH）水平增加。增强的谷氨酰胺摄取也用于为三羧酸（TCA）循环提供动力，以维持UGCG过表达细胞的增殖优势。我们的数据揭示了乳腺癌细胞中GSL和谷氨酰胺代谢之间的联系，据我们所知，这是鞘脂研究领域中的一种新的相关性。
UDP-glucose ceramide glucosyltransferase (UGCG) is the key enzyme in glycosphingolipid (GSL) metabolism by being the only enzyme that generates glucosylceramide (GlcCer) de novo. Increased UGCG synthesis is associated with pro-cancerous processes such as increased proliferation and multidrug resistance in several cancer types. We investigated the influence of UGCG overexpression on glutamine metabolism in breast cancer cells. We observed adapted glucose and glutamine uptake in a limited energy supply environment following UGCG overexpression. Glutamine is used for reinforced oxidative stress response shown by increased mRNA expression of glutamine metabolizing proteins such as glutathione-disulfide reductase (GSR) resulting in increased reduced glutathione (GSH) level. Augmented glutamine uptake is also used for fueling the tricarboxylic acid (TCA) cycle to maintain the proliferative advantage of UGCG overexpressing cells. Our data reveal a link between GSL and glutamine metabolism in breast cancer cells, which is to our knowledge a novel correlation in the field of sphingolipid research.