G6PD promotes renal cell carcinoma proliferation through positive feedback regulation of p-STAT3.
G6PD promotes renal cell carcinoma proliferation through positive feedback regulation of p-STAT3.
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G6PD通过p-STAT3的正反馈调节促进肾细胞癌增殖
DOI：
10.18632/oncotarget.22566
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发表时间：
2017-12-12
期刊：
影响因子：
--
通讯作者：
Zhu Y
中科院分区：
文献类型：
--
作者：
Zhang Q;Yang Z;Han Q;Bai H;Wang Y;Yi X;Yi Z;Yang L;Jiang L;Song X;Kuang Y;Zhu Y
异位葡萄糖6-磷酸脱氢酶(G6PD)的表达在肿瘤细胞代谢重编程中起重要作用，导致多种恶性肿瘤预后不良。我们先前的研究表明，G6PD在肾透明细胞癌(CcRCC)中过表达，CcRCC是肾细胞癌最常见的亚型。然而，它在RCC中的作用仍不清楚。在这里，我们证明了G6PD不仅在所有类型的肾癌标本中上调，而且在肾癌细胞系中也显示出更高的活性。G6PD过表达促进了肾癌细胞的增殖，改变了细胞周期分布，促进了异种移植肾癌的发展。G6PD通过促进NADPH依赖的NOX4活化，从而上调ROS的产生，从而导致p-STAT3和CyClinD1表达增加。增强的ROS生成挽救了G6PD基因敲除细胞中p-STAT3和CyClinD1表达的下调，而ROS清除剂则逆转了G6PD过表达细胞中上调的p-STAT3和CyClinD1的表达。此外，p-STAT3通过与G6PD启动子结合来激活G6PD基因的表达，表明p-STAT3对G6PD的过度表达形成了一个正反馈调控环。G6PD的表达受p-STAT3激活剂或抑制剂的影响而上调或下调。因此，G6PD可能是肾癌治疗的有效靶点。
Ectopic Glucose 6-phosphate dehydrogenase (G6PD) expression plays important role in tumor cell metabolic reprogramming and results in poor prognosis of multiple malignancies. Our previous study indicated that G6PD is overexpressed in clear cell renal cell carcinoma (ccRCC), the most common subtype of RCC. However, its role in RCC is still unclear. Here, we demonstrate that G6PD is not only up-regulated in all types of RCC specimens but also displays higher activities in RCC cell lines. G6PD overexpression promoted RCC cell proliferation, altered cell cycle distribution, and enhanced xenografted RCC development. G6PD up-regulated ROS generation by facilitating NADPH-dependent NOX4 activation, which led to increased expression of p-STAT3 and CyclinD1. Enhanced ROS generation rescued the p-STAT3 and CyclinD1 expression reduction in G6PD-knockdown cells, while ROS scavengers reversed the up-regulated p-STAT3 and CyclinD1 expression in G6PD-overexpressing cells. Furthermore, p-STAT3 activated G6PD gene expression via binding to the G6PD promoter, demonstrating that p-STAT3 forms a positive feedback regulatory loop for G6PD overexpression. G6PD expression was up or down-regulated in response to the impact of p-STAT3 activators or inhibitors. Therefore, G6PD may be an effective RCC therapeutic target.
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影响因子：
7.4
作者：
Chinello C;Cazzaniga M;De Sio G;Smith AJ;Grasso A;Rocco B;Signorini S;Grasso M;Bosari S;Zoppis I;Mauri G;Magni F
通讯作者：
Magni F
二氢杨梅素通过 ROS-STAT3 信号促进头颈鳞状细胞癌的自噬和凋亡
影响因子：
--
作者：
Fan TF;Wu TF;Bu LL;Ma SR;Li YC;Mao L;Sun ZJ;Zhang WF
通讯作者：
Zhang WF
NADPH 氧化酶 NOX4 通过促进 HIF2α 的表达和核积累来支持肾肿瘤发生。
影响因子：
11.2
作者：
Gregg JL;Turner RM 2nd;Chang G;Joshi D;Zhan Y;Chen L;Maranchie JK
通讯作者：
Maranchie JK
影响因子：
8.8
作者：
通讯作者：
--
影响因子：
64.5
作者：
Bromberg, JF;Wrzeszczynska, MH;Darnell, JE
通讯作者：
Darnell, JE