FOXM1 promotes reprogramming of glucose metabolism in epithelial ovarian cancer cells via activation of GLUT1 and HK2 transcription.
FOXM1 promotes reprogramming of glucose metabolism in epithelial ovarian cancer cells via activation of GLUT1 and HK2 transcription.
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FOXM1 通过激活 GLUT1 和 HK2 转录促进上皮性卵巢癌细胞中葡萄糖代谢的重编程
DOI：
10.18632/oncotarget.10103
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发表时间：
2016-07-26
期刊：
影响因子：
--
通讯作者：
Li Y
中科院分区：
文献类型：
--
作者：
Wang Y;Yun Y;Wu B;Wen L;Wen M;Yang H;Zhao L;Liu W;Huang S;Wen N;Li Y
癌细胞主要通过有氧糖酵解表现出重编程代谢，这种现象在历史上被称为瓦尔堡效应;然而，其潜在机制在很大程度上仍然未知。在这项研究中，我们的特点是转录因子叉头盒蛋白M1（FOXM 1）在有氧糖酵解的人上皮性卵巢癌（EOC）及其分子机制的关键作用。我们的数据显示FOXM 1的异常表达显著促进了EOC细胞中葡萄糖代谢的重编程。当FOXM 1基因表达被RNA干扰抑制时，EOC细胞有氧糖酵解和细胞增殖被下调。此外，FOXM 1在EOC细胞中的敲低显着降低葡萄糖转运蛋白1（GLUT 1）和己糖激酶2（HK 2）的表达。FOXM 1直接与GLUT 1和HK 2启动子区域结合，并在转录水平调节启动子活性和基因表达。这揭示了FOXM 1调节葡萄糖代谢的新机制。更重要的是，我们进一步证实FOXM 1、GLUT 1和HK 2的表达水平在人EOC组织中相对于正常卵巢组织显著增加，并且FOXM 1表达与GLUT 1和HK 2表达正相关。综上所述，我们的研究结果表明，FOXM 1通过激活GLUT 1和HK 2转录促进EOC细胞中葡萄糖代谢的重编程，这表明FOXM 1可能是开发新型抗癌药物的有氧糖酵解途径的重要靶点。
Cancer cells exhibit the reprogrammed metabolism mainly via aerobic glycolysis, a phenomenon known historically as the Warburg effect; however, the underlying mechanisms remain largely unknown. In this study, we characterized the critical role of transcription factor Forkhead box protein M1 (FOXM1) in aerobic glycolysis of human epithelial ovarian cancer (EOC) and its molecular mechanisms. Our data showed that aberrant expression of FOXM1 significantly contributed to the reprogramming of glucose metabolism in EOC cells. Aerobic glycolysis and cell proliferation were down-regulated in EOC cells when FOXM1 gene expression was suppressed by RNA interference. Moreover, knockdown of FOXM1 in EOC cells significantly reduced glucose transporter 1 (GLUT1) and hexokinase 2 (HK2) expression. FOXM1 bound directly to the GLUT1 and HK2 promoter regions and regulated the promoter activities and the expression of the genes at the transcriptional level. This reveals a novel mechanism by which glucose metabolism is regulated by FOXM1. Importantly, we further demonstrated that the expression levels of FOXM1, GLUT1 and HK2 were significantly increased in human EOC tissues relative to normal ovarian tissues, and that FOXM1 expression was positively correlated with GLUT1 and HK2 expression. Taken together, our results show that FOXM1 promotes reprogramming of glucose metabolism in EOC cells via activation of GLUT1 and HK2 transcription, suggesting that FOXM1 may be an important target in aerobic glycolysis pathway for developing novel anticancer agents.
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FOXM1 通过 LDHA 表达的反式激活促进瓦尔堡效应和胰腺癌进展。
DOI：
10.1158/1078-0432.ccr-13-2407
发表时间：
2014-05-15
期刊：
Clinical cancer research : an official journal of the American Association for Cancer Research
影响因子：
--
作者：
Cui J;Shi M;Xie D;Wei D;Jia Z;Zheng S;Gao Y;Huang S;Xie K
通讯作者：
Xie K
影响因子：
21.3
作者：
Laoukili, J;Kooistra, MRH;Medema, RH
通讯作者：
Medema, RH
DOI：
10.1007/s00259-006-0260-x
发表时间：
2007-04-01
影响因子：
9.1
作者：
Chung, Hyun Hoon;Kang, Won Jun;Lee, Hyo-Pyo
通讯作者：
Lee, Hyo-Pyo
影响因子：
11.2
作者：
Huang C;Qiu Z;Wang L;Peng Z;Jia Z;Logsdon CD;Le X;Wei D;Huang S;Xie K
通讯作者：
Xie K
影响因子：
11.2
作者：
Kong X;Li L;Li Z;Le X;Huang C;Jia Z;Cui J;Huang S;Wang L;Xie K
通讯作者：
Xie K