Enolase 1 stimulates glycolysis to promote chemoresistance in gastric cancer.
Enolase 1 stimulates glycolysis to promote chemoresistance in gastric cancer.
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烯醇化酶 1 刺激糖酵解促进胃癌化疗耐药
DOI：
10.18632/oncotarget.17868
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发表时间：
2017-07-18
期刊：
影响因子：
--
通讯作者：
Jin H
中科院分区：
文献类型：
--
作者：
Qian X;Xu W;Xu J;Shi Q;Li J;Weng Y;Jiang Z;Feng L;Wang X;Zhou J;Jin H
化疗是早期和晚期癌症治疗的主要选择。然而，内在或获得性耐药严重制约了化疗的临床疗效。开发检测和克服耐药性的新方法至关重要。在这项研究中，我们证明了加速糖酵解在胃癌细胞的内在和获得性顺铂耐药中都起着关键作用。顺铂耐药细胞的代谢重编程以糖酵解依赖性增加为特征。通过葡萄糖饥饿或2-脱氧- d -葡萄糖（2-DG）治疗抑制糖酵解可显著逆转耐药性。通过蛋白质组学筛选，我们发现糖酵解酶烯醇化酶1 （ENO1）在顺铂耐药胃癌细胞中的表达增加。siRNA耗尽ENO1显著减少糖酵解并逆转耐药。此外，ENO1表达的增加归因于ENO1靶向miR-22的下调，而不是激活基因转录或延长蛋白稳定性。最后，ENO1蛋白水平升高与胃癌患者总生存期缩短有关。综上所述，ENO1是一种预测胃癌耐药及整体预后的新型生物标志物。通过化学抑制剂靶向ENO1或上调miR-22可能对克服耐药有价值。
Chemotherapy is the major choice for the cancer treatment of early and advanced stages. However, intrinsic or acquired drug resistance significantly restricts the clinical efficacy of chemotherapy. It is critical to develop novel approaches to detect and overcome drug resistance. In this study, we demonstrated that accelerated glycolysis played a pivotal role in both intrinsic and acquired cisplatin-resistance of gastric cancer cells. The metabolic reprogramming of cisplatin-resistant cells was characterized by increased glycolysis dependence. Inhibition of glycolysis with glucose starvation or 2-Deoxy-D-glucose (2-DG) treatment significantly reversed drug resistance. By proteomic screening, we found the increased expression of the glycolytic enzyme Enolase 1 (ENO1) in cisplatin-resistant gastric cancer cells. Depletion of ENO1 by siRNA significantly reduced glycolysis and reversed drug resistance. Moreover, the increased expression of ENO1 was attributed to the down-regulation of ENO1-targeting miR-22, rather than activated gene transcriptional or prolonged protein stability. Finally, the elevated levels of ENO1 proteins were associated with the shorter overall survival of gastric cancer patients. In conclusion, ENO1 is a novel biomarker to predict drug resistance and overall prognosis in gastric cancer. Targeting ENO1 by chemical inhibitors or up-regulating miR-22 could be valuable to overcome drug resistance.
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影响因子：
20.3
作者：
McBrayer, Samuel K.;Cheng, Javelin C.;Shanmugam, Mala
通讯作者：
Shanmugam, Mala
DOI：
10.1016/j.bbrc.2012.05.063
发表时间：
2012-06-22
影响因子：
3.1
作者：
Kwon, Oh-Hyung;Kang, Tae-Wook;Kim, Yong Sung
通讯作者：
Kim, Yong Sung
影响因子：
11.5
作者：
De Rosa, Viviana;Iommelli, Francesca;Del Vecchio, Silvana
通讯作者：
Del Vecchio, Silvana
影响因子：
9.7
作者：
Lu, Jianrong;Tan, Ming;Cai, Qingsong
通讯作者：
Cai, Qingsong
DOI：
10.1016/j.jconrel.2011.03.032
发表时间：
2011-10-30
期刊：
Journal of controlled release : official journal of the Controlled Release Society
影响因子：
--
作者：
Milane L;Ganesh S;Shah S;Duan ZF;Amiji M
通讯作者：
Amiji M