Glucose-6-phosphate dehydrogenase and NADPH oxidase 4 control STAT3 activity in melanoma cells through a pathway involving reactive oxygen species, c-SRC and SHP2
机构：[1]Department of Biochemistry and Molecular Biology, Kunming Medical University, Kunming 650500, China[2]The First Hospital affiliated to Kunming Medical University, Kunming 650032, China昆明医科大学附属第一医院[3]The Maternal and Child Health Hospital of Yunnan Province, Kunming 650051, China.
Background: Glucose-6-phosphate dehydrogenase (G6PD) participates in glucose utilization by catalysing the first step of the pentose-phosphate pathway in mammalian cells. Previous studies have shown that changes in G6PD levels can promote tumor cell proliferation or apoptosis via the STAT3/5 pathway in a human melanoma xenograft model. G6PD cooperates with NADPH oxidase 4 (NOX4) in the cellular metabolism of reactive oxygen species (ROS) and in maintaining the intracellular redox state. Methods: In this study, the effect of G6PD or NOX4 silencing in the melanoma line A375 was examined in terms of redox state, proto-oncogene tyrosine-protein kinase Src (c-Src) and the tyrosine-specific protein phosphatase SHP2 expression as well as cell cycle progression. Results: The results demonstrate that: (1) Downregulation of cyclin D1 and CDK4 and up-regulation of p53 and p21 occurred in response to silencing of G6PD and NOX4 thus resulting in G1/S cell cycle arrest and inhibition of A375 cell proliferation. (2) The blockade of cell proliferation is primarily due to a reduced DNA-binding activity of STAT3. (3) The DNA-binding activity of STAT3 was regulated by the upstream factors, c-SRC and SHP2. Silencing of NOX4 in A375 cells inhibited c-SRC and SHP2 regulated STAT3 activity. Conclusion: The data are consistent with a novel G6PD-NOX4-NADPH-ROS-c-SRC/SHP2 pathway controlling STAT3 activity in A375 melanoma cells.
基金：
This work was supported by a grant from the
National Natural Science Foundation of China
(no. 81160246 and 81460421) and Yunnan
Provincial Science and Technology Foundation
(no. 2013FB102).
语种：
外文
中科院(CAS)分区：
出版当年[2016]版：
大类|2 区医学
小类|3 区肿瘤学
最新[2023]版：
大类|3 区医学
小类|3 区肿瘤学
第一作者：
第一作者机构：[1]Department of Biochemistry and Molecular Biology, Kunming Medical University, Kunming 650500, China
共同第一作者：
通讯作者：
通讯机构：[1]Department of Biochemistry and Molecular Biology, Kunming Medical University, Kunming 650500, China[*1]Department of Biochemistry and Molecular Biology, Kunming Medical University, No. 191, West Renming Road, Kunming 650500, China.
推荐引用方式(GB/T 7714)：
Tianchi Cai,Yingmin Kuang,Chunhua Zhang,et al.Glucose-6-phosphate dehydrogenase and NADPH oxidase 4 control STAT3 activity in melanoma cells through a pathway involving reactive oxygen species, c-SRC and SHP2[J].American Journal of Cancer Research.2015,5(5):
APA：
Tianchi Cai,Yingmin Kuang,Chunhua Zhang,Zheng Zhang,Long Chen...&Yuechun Zhu.(2015).Glucose-6-phosphate dehydrogenase and NADPH oxidase 4 control STAT3 activity in melanoma cells through a pathway involving reactive oxygen species, c-SRC and SHP2.American Journal of Cancer Research,5,(5)
MLA：
Tianchi Cai,et al."Glucose-6-phosphate dehydrogenase and NADPH oxidase 4 control STAT3 activity in melanoma cells through a pathway involving reactive oxygen species, c-SRC and SHP2".American Journal of Cancer Research 5..5(2015)
