Research Papers:

Hexokinase 2 enhances the metastatic potential of tongue squamous cell carcinoma via the SOD2-H2O2 pathway

Wei Wang _, Zhonghua Liu, Luodan Zhao, Jingjing Sun, Qianting He, Wangxiang Yan, Zhiyuan Lu and Anxun Wang

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Oncotarget. 2017; 8:3344-3354. https://doi.org/10.18632/oncotarget.13763

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Wei Wang1,*, Zhonghua Liu1,*, Luodan Zhao2,1,*, Jingjing Sun1, Qianting He1, Wangxiang Yan1, Zhiyuan Lu1, Anxun Wang1

1Department of Oral and Maxillofacial Surgery, First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, Guangdong, 510080, China

2Department of Stomatology, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, Guangdong, 510120, China

*These authors have contributed equally to this work

Correspondence to:

Anxun Wang, email: [email protected]

Keywords: tongue squamous cell carcinoma, hexokinase, glycolysis, metastasis, manganese superoxide dismutase (SOD2)

Received: September 27, 2016     Accepted: November 16, 2016     Published: December 01, 2016


The glycolytic enzyme hexokinase (HK2), which is aberrantly expressed in various types of tumours, is associated with metastasis. However, its role in the progression and metastasis of tongue squamous cell carcinoma (TSCC) remains unclear. The results of our study showed that HK2 expression is often deregulated in TSCC patients. Increased HK2 expression was associated with tumour stage, clinical stage, lymph node metastasis, but not pathological grade, and reduced overall survival. Microarray and western blotting analyses revealed increases in HK2 expression in TSCC cells with higher metastatic potential. The following effects were observed with HK2 knockdown: inhibition of cell migration and invasion; reduced SOD2 activity and intracellular H2O2 levels; suppression of pERK1/2, Slug and Vimentin expression; and inhibition of tumour growth and lung metastasis in vivo. Conversely, HK2 overexpression promoted cell migration and invasion, increased SOD2 activity and intracellular H2O2, and enhanced expression of pERK1/2, Slug and Vimentin. Thus, our results demonstrate that deregulation of HK2 expression has an important function in the progression of TSCC and may serve as a biomarker of its metastatic potential in TSCC patients. HK2 enhances the metastatic potential of TSCC by stimulating the SOD2-H2O2 pathway.

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