UGCG overexpression leads to increased glycolysis and increased oxidative phosphorylation of breast cancer cells
UGCG overexpression leads to increased glycolysis and increased oxidative phosphorylation of breast cancer cells
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DOI：
10.1038/s41598-020-65182-y
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发表时间：
2020-05-18
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;Gruber，Lisa;Wegner，Marthe-Susanna
鞘糖脂 (GSL) 代谢途径中唯一从头产生葡萄糖神经酰胺 (GlcCer) 的酶是 UDP-葡萄糖神经酰胺葡萄糖基转移酶 (UGCG)。 UGCG 与促癌过程有关，例如多种癌症类型的多药耐药性发展和增殖增加。此前，我们展示了 UGCG 依赖性谷氨酰胺代谢对乳腺癌细胞营养不良环境的适应。这种适应包括增强氧化应激反应并通过增加谷氨酰胺氧化来促进三羧酸（TCA）循环。在当前的研究中，我们研究了 UGCG 过度表达（OE）后的糖酵解和氧化代谢表型。 UGCG 过表达的 MCF-7 细胞通过增加糖酵解和氧化葡萄糖代谢，经历了从静止/有氧代谢到能量代谢的代谢转变。精力充沛的代谢表型与线粒体质量增加无关，但线粒体周转标记物增加。 UGCG OE 改变了内质网 (ER)/线粒体部分的鞘脂组成，这可能有助于增加线粒体周转和增加细胞代谢。我们的数据表明 GSL 与细胞能量代谢密切相关，这一发现可能有助于开发新的癌症治疗策略。
The only enzyme in theglycosphingolipid(GSL) metabolic pathway, which producesglucosylceramide(GlcCer)de novoisUDP-glucose ceramide glucosyltransferase(UGCG). UGCG is linked to pro-cancerous processes such as multidrug resistance development and increased proliferation in several cancer types. Previously, we showed an UGCG-dependent glutamine metabolism adaption to nutrient-poor environment of breast cancer cells. This adaption includes reinforced oxidative stress response and fueling thetricarboxylic acid(TCA) cycle by increased glutamine oxidation. In the current study, we investigated glycolytic and oxidative metabolic phenotypes following UGCGoverexpression(OE). UGCG overexpressing MCF-7 cells underwent a metabolic shift from quiescent/aerobic to energetic metabolism by increasing both glycolysis and oxidative glucose metabolism. The energetic metabolic phenotype was not associated with increased mitochondrial mass, however, markers of mitochondrial turnover were increased. UGCG OE altered sphingolipid composition of theendoplasmic reticulum(ER)/mitochondria fractions that may contribute to increased mitochondrial turnover and increased cell metabolism. Our data indicate that GSL are closely connected to cell energy metabolism and this finding might contribute to development of novel therapeutic strategies for cancer treatment.