Pyruvate kinase M2 deregulation enhances the metastatic potential of tongue squamous cell carcinoma.
Pyruvate kinase M2 deregulation enhances the metastatic potential of tongue squamous cell carcinoma.
复制标题
丙酮酸激酶 M2 失调增强舌鳞状细胞癌的转移潜力
DOI：
10.18632/oncotarget.19291
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发表时间：
2017-09-15
期刊：
影响因子：
--
通讯作者：
Wang A
中科院分区：
文献类型：
--
作者：
Wang W;He Q;Sun J;Liu Z;Zhao L;Lu Z;Zhou X;Wang A
丙酮酸激酶M2(PKM2)已被证实与多种癌症的预后有关。然而，它在舌鳞状细胞癌(TSCC)的发生和转移中的作用尚不清楚。免疫组织化学(IHC)结果证实PKM2在TSCC中高表达。PKM2表达上调与淋巴结转移有关，并与总生存期降低有关。基因芯片分析和Western blotts结果显示，在转移潜能增强的TSCC细胞中，PKM2的表达上调。在体内，PKM2基因敲除可抑制细胞迁移和侵袭，降低细胞内超氧化物歧化酶SOD2活性和细胞内过氧化氢水平，抑制肿瘤生长和肺转移。PKM2过表达促进细胞迁移和侵袭，增加SOD2活性和细胞内过氧化氢水平。此外，miR-138直接靶向PKM2并抑制PKM2的表达。因此，PKM2的失控在TSCC中起着重要作用，可作为TSCC患者转移潜能的生物标志物或治疗靶点。作为miR-138靶基因，PKM2通过SOD2-H_2O_2途径增强TSCC的转移潜能。
Pyruvate kinase M2 (PKM2) has been verified to correlate with the prognosis of many types of cancer. However, its role in the development and metastasis of tongue squamous cell carcinoma (TSCC) remains unclear. The immunohistochemistry (IHC) results confirmed that PKM2 is overexpressed in patients with TSCC. PKM2 up-regulation was related to lymph node metastasis and associated with reduced overall survival. According to the microarray analysis and Western blots, PKM2 expression was up-regulated in TSCC cells with enhanced metastatic potential. PKM2 knockdown inhibited cell migration and invasion, reduced SOD2 (manganese superoxide dismutase) activity and the intracellular H2O2 level, and inhibited tumour growth and lung metastasis in vivo. PKM2 overexpression promoted cell migration and invasion, and increased SOD2 activity and the intracellular H2O2 level. Moreover, miR-138 directly targeted PKM2 and inhibited PKM2 expression. Thus, PKM2 deregulation plays an important role in TSCC and may serve as a biomarker of metastatic potential or as a therapeutic target in patients with TSCC. PKM2, a miR-138 target gene, enhances the metastatic potential of TSCC through the SOD2-H2O2 pathway.