Glutamate-Oxaloacetate Transaminase 1 Impairs Glycolysis by Interacting with Pyruvate Carboxylase and Further Inhibits the Malignant Phenotypes of Glioblastoma Cells
Glutamate-Oxaloacetate Transaminase 1 Impairs Glycolysis by Interacting with Pyruvate Carboxylase and Further Inhibits the Malignant Phenotypes of Glioblastoma Cells
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谷氨酸-草酰乙酸转氨酶 1 通过与丙酮酸羧化酶相互作用损害糖酵解，并进一步抑制胶质母细胞瘤细胞的恶性表型
DOI：
10.1016/j.wneu.2021.07.097
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发表时间：
2021
影响因子：
2
通讯作者：
Ming Chen
中科院分区：
文献类型：
--
作者：
Tianchi Tang;Yang Liu;Min Yang;Ming Tu;Wanchun Zhu;Ming Chen
背景糖酵解是多形性胶质母细胞瘤（GBM）快速生长的重要代谢方式。已有研究表明，谷草转氨酶1（GOT 1）在GBM中低表达，GOT 1高表达的患者预后较好。然而，GOT 1对GBM细胞糖酵解和恶性表型的影响及其机制尚不清楚。分析不同GOT 1水平患者的临床资料及预后。GOT 1被敲低或过表达后，测量葡萄糖消耗、乳酸和丙酮酸的产生。采用Western blot、CCK-8法和流式细胞术分析GOT 1对GBM细胞恶性表型的影响。结果GBM中GOT 1表达较低，GOT 1高表达者生存期较长。过表达GOT 1抑制GBM细胞的糖酵解和恶性表型。2-DG治疗可以部分逆转GOT 1基因敲除引起的恶性表型增强。GOT 1的表达与PC呈正相关。结论GOT 1通过与PC相互作用，抑制GBM细胞糖酵解，进而抑制GBM细胞的恶性表型。
BackgroundGlycolysis is an important metabolic manner in glioblastoma multiforme (GBM)'s rapid growth. It has been reported that glutamate-oxaloacetate transaminase 1 (GOT1) is low-expressed in GBM and patients with high-expressed GOT1 have better prognosis. However, the effect and mechanism of GOT1 on glycolysis and malignant phenotypes of GBM cells are still unclear.MethodsThe expression differences of GOT1 between GBM parenchyma and adjacent tissues were detected. The prognosis and clinical data with different levels of GOT1 were also analyzed. The glucose consumption, production of lactate and pyruvate were measured after GOT1 was knocked down or overexpressed. The effects of GOT1 on GBM cell's malignant phenotypes were analyzed by Western blot, CCK-8 assay, and flow cytometry. The relationship between GOT1 and pyruvate carboxylase (PC) was examined by immunoprecipitation and immunofluorescence.ResultsGOT1 was expressed little in GBM, and patients with highly expressed GOT1 had longer survival periods. Overexpressed GOT1 inhibited the glycolysis and malignant phenotypes of GBM cells. 2-DG treatment could partially reverse the enhancement of malignant phenotypes caused by knockdown of GOT1. The expression of GOT1 was positively correlated with PC. The inhibitory effect of GOT1 on glycolysis could be partially reversed by PC's knockdown.ConclusionsGOT1 could impair glycolysis by interacting with PC and further inhibit the malignant phenotypes of GBM cells.