Oncotarget

Research Papers:

Enolase 1 stimulates glycolysis to promote chemoresistance in gastric cancer

Xiaoling Qian, Wenxia Xu, Jinye Xu, Qiqi Shi, Jiaqiu Li, Yu Weng, Zhinong Jiang, Lifeng Feng, Xian Wang, Jianwei Zhou and Hongchuan Jin _

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Oncotarget. 2017; 8:47691-47708. https://doi.org/10.18632/oncotarget.17868

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Abstract

Xiaoling Qian1,*, Wenxia Xu1,*, Jinye Xu1, Qiqi Shi1, Jiaqiu Li2, Yu Weng3, Zhinong Jiang4, Lifeng Feng1, Xian Wang2, Jianwei Zhou5 and Hongchuan Jin1

1Laboratory of Cancer Biology, Key Lab of Biotherapy in Zhejiang, Sir Run Run Shaw Hospital, Medical School of Zhejiang University, Zhejiang, China

2Department of Medical Oncology, Sir Run Run Shaw Hospital, Medical School of Zhejiang University, Zhejiang, China

3Department of Clinical Medicine, Sir Run Run Shaw Hospital, Medical School of Zhejiang University, Zhejiang, China

4Department of Pathology, Sir Run Run Shaw Hospital, Medical School of Zhejiang University, Zhejiang, China

5Department of Molecular Cell Biology and Toxicology, School of Public Health, Nanjing Medical University, Nanjing, China

*These authors contributed equally to this work

Correspondence to:

Hongchuan Jin, email: jinhc@zju.edu.cn

Keywords: enolase 1, cisplatin-resistance, glycolysis, gastric cancer, miRNA-22

Received: February 07, 2017     Accepted: April 27, 2017     Published: May 15, 2017

ABSTRACT

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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