2-Deoxyglucose Suppresses ERK Phosphorylation in LKB1 and Ras Wild-Type Non-Small Cell Lung Cancer Cells.
2-Deoxyglucose Suppresses ERK Phosphorylation in LKB1 and Ras Wild-Type Non-Small Cell Lung Cancer Cells.
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2-脱氧葡萄糖抑制 LKB1 和 Ras 野生型非小细胞肺癌细胞中的 ERK 磷酸化
DOI：
10.1371/journal.pone.0168793
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发表时间：
2016
期刊：
影响因子：
3.7
通讯作者：
Zhong D
中科院分区：
文献类型：
--
作者：
Sun L;Liu X;Fu H;Zhou W;Zhong D
肿瘤细胞依靠有氧糖酵解产生ATP，即“Warburg”效应。2-脱氧葡萄糖（2-DG）是一种糖酵解抑制剂，但其对细胞信号通路的影响尚未完全阐明。在此，我们试图研究2-DG对肺癌细胞ERK功能的影响。我们发现2-DG在肺癌细胞中以时间和剂量依赖的方式抑制ERK磷酸化。这种抑制需要功能性的LKB1。LKB1野生型细胞中LKB1敲低与p-ERK基础水平升高相关。在LKB1缺失的细胞中恢复LKB1可显著抑制ERK的激活。用AMPK抑制剂、AMPK siRNA或DN-AMPK阻断AMPK功能可降低2-DG对ERK的抑制作用，提示2-DG诱导的ERK抑制是由LKB1/AMPK信号介导的。此外，igf1诱导的ERK磷酸化被2-DG显著降低。相反，ERK的主要上游调控因子K-Ras的一部分致癌突变体会阻断2- dg诱导的LKB1/AMPK信号传导。这些发现揭示了LKB1/AMPK和ERK信号之间潜在的串扰，并有助于更好地理解2-DG的作用机制。
Tumor cells rely on aerobic glycolysis to generate ATP, namely the "Warburg" effect. 2-deoxyglucose (2-DG) is well characterized as a glycolytic inhibitor, but its effect on cellular signaling pathways has not been fully elucidated. Herein, we sought to investigate the effect of 2-DG on ERK function in lung cancer cells. We found that 2-DG inhibits ERK phosphorylation in a time and dose-dependent manner in lung cancer cells. This inhibition requires functional LKB1. LKB1 knockdown in LKB1 wildtype cells correlated with an increase in the basal level of p-ERK. Restoration of LKB1 in LKB1-null cells significantly inhibits ERK activation. Blocking AMPK function with AMPK inhibitor, AMPK siRNA or DN-AMPK diminishes the inhibitory effect of 2-DG on ERK, suggesting that 2-DG—induced ERK inhibition is mediated by LKB1/AMPK signaling. Moreover, IGF1-induced ERK phosphorylation is significantly decreased by 2-DG. Conversely, a subset of oncogenic mutants of K-Ras, the main upstream regulator of ERK, blocks 2-DG—induced LKB1/AMPK signaling. These findings reveal the potential cross-talk between LKB1/AMPK and ERK signaling and help to better understand the mechanism of action of 2-DG.
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影响因子：
13.8
作者：
Liberti MV;Locasale JW
通讯作者：
Locasale JW
DOI：
10.1038/nrc3106
发表时间：
2011-10-13
期刊：
Nature reviews. Cancer
影响因子：
--
作者：
通讯作者：
--
影响因子：
64.8
作者：
Ji, Hongbin;Ramsey, Matthew R.;Wong, Kwok-Kin
通讯作者：
Wong, Kwok-Kin
影响因子：
5.7
作者：
Kurtoglu, Metin;Gao, Ningguo;Lampidis, Theodore J.
通讯作者：
Lampidis, Theodore J.
DOI：
10.1016/s0360-3016(96)85017-6
发表时间：
1996-04-01
影响因子：
7
作者：
Mohanti, BK;Rath, GK;Jain, V
通讯作者：
Jain, V