Hexokinase 2 enhances the metastatic potential of tongue squamous cell carcinoma via the SOD2-H2O2 pathway.
Hexokinase 2 enhances the metastatic potential of tongue squamous cell carcinoma via the SOD2-H2O2 pathway.
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己糖激酶2通过SOD2-H2O2途径增强舌鳞状细胞癌的转移潜力
DOI：
10.18632/oncotarget.13763
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发表时间：
2017-01-10
期刊：
影响因子：
--
通讯作者：
Wang A
中科院分区：
文献类型：
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作者：
Wang W;Liu Z;Zhao L;Sun J;He Q;Yan W;Lu Z;Wang A
糖酵解酶己糖激酶（HK 2）在各种类型的肿瘤中异常表达，与转移有关。然而，其在舌鳞状细胞癌（TSCC）的进展和转移中的作用仍不清楚。我们的研究结果表明，HK 2的表达往往是失调的TSCC患者。HK 2表达增加与肿瘤分期、临床分期、淋巴结转移相关，但与病理分级无关，并降低总生存率。微阵列和蛋白质印迹分析显示，在具有较高转移潜能的TSCC细胞中，HK 2表达增加。HK 2敲低后观察到以下效应：抑制细胞迁移和侵袭;降低SOD 2活性和细胞内H2 O2水平;抑制pERK 1/2、Slug和波形蛋白表达;抑制体内肿瘤生长和肺转移。相反，HK 2过表达促进细胞迁移和侵袭，增加SOD 2活性和细胞内H2 O2，并增强pERK 1/2、Slug和Vimentin的表达。因此，我们的研究结果表明，HK 2表达失调在TSCC的进展中具有重要的作用，并可能作为其在TSCC患者中转移潜力的生物标志物。HK 2通过刺激SOD 2-H2 O2通路增强TSCC的转移潜能。
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.