title: Hexokinase 2 enhances the metastatic potential of tongue squamous cell carcinoma via the SOD2-H2O2 pathway.
abstract: 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.
authors.affiliation: Department of Oral and Maxillofacial Surgery, First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, Guangdong, 510080, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Wang
authors.affiliation: Department of Oral and Maxillofacial Surgery, First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, Guangdong, 510080, China.
authors.forename: Zhonghua
authors.initials: Z
authors.lastname: Liu
authors.affiliation: Department of Stomatology, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, Guangdong, 510120, China.|Department of Oral and Maxillofacial Surgery, First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, Guangdong, 510080, China.
authors.forename: Luodan
authors.initials: L
authors.lastname: Zhao
authors.affiliation: Department of Oral and Maxillofacial Surgery, First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, Guangdong, 510080, China.
authors.forename: Jingjing
authors.initials: J
authors.lastname: Sun
authors.affiliation: Department of Oral and Maxillofacial Surgery, First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, Guangdong, 510080, China.
authors.forename: Qianting
authors.initials: Q
authors.lastname: He
authors.affiliation: Department of Oral and Maxillofacial Surgery, First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, Guangdong, 510080, China.
authors.forename: Wangxiang
authors.initials: W
authors.lastname: Yan
authors.affiliation: Department of Oral and Maxillofacial Surgery, First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, Guangdong, 510080, China.
authors.forename: Zhiyuan
authors.initials: Z
authors.lastname: Lu
authors.affiliation: Department of Oral and Maxillofacial Surgery, First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, Guangdong, 510080, China.
authors.forename: Anxun
authors.initials: A
authors.lastname: Wang
mesh_terms: D000818:Animals; D002294:Carcinoma, Squamous Cell / Q000235:genetics / Q000378:metabolism* / Q000401:mortality / Q000473:pathology*; D045744:Cell Line, Tumor; D002465:Cell Movement; D004195:Disease Models, Animal; D005786:Gene Expression Regulation; D055785:Gene Knockdown Techniques; D064593:Heterografts; D006593:Hexokinase / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D006861:Hydrogen Peroxide / Q000378:metabolism*; D008297:Male; D053858:Metabolic Networks and Pathways; D051379:Mice; D009362:Neoplasm Metastasis; D012189:Retrospective Studies; D015398:Signal Transduction; D013482:Superoxide Dismutase / Q000378:metabolism*; D014062:Tongue Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000401:mortality / Q000473:pathology*; D000099156:Superoxide Dismutase 2
chemical_list: D006593:Hexokinase; D006861:Hydrogen Peroxide; D013482:Superoxide Dismutase; D000099156:Superoxide Dismutase 2
keywords: glycolysis; hexokinase; manganese superoxide dismutase (SOD2); metastasis; tongue squamous cell carcinoma