Pyruvate kinase M2 deregulation enhances the metastatic potential of tongue squamous cell carcinoma

丙酮酸激酶M2失调增强舌鳞状细胞癌的转移潜能

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Abstract

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 H(2)O(2) level, and inhibited tumour growth and lung metastasis in vivo. PKM2 overexpression promoted cell migration and invasion, and increased SOD2 activity and the intracellular H(2)O(2) 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-H(2)O(2) pathway.

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