Pyruvate kinase M2 deregulation enhances the metastatic potential of tongue squamous cell carcinoma
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Wei Wang1,*, Qianting He1,*, Jingjing Sun1,*, Zhonghua Liu1, Luodan Zhao1, Zhiyuan Lu1, Xiaofeng Zhou2,3 and Anxun Wang1
1Department of Oral and Maxillofacial Surgery, First Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong 510080, China
2Center for Molecular Biology of Oral Diseases, Department of Periodontics, College of Dentistry, University of Illinois at Chicago, Chicago, IL 60612-7213, USA
3UIC Cancer Center, Graduate College, University of Illinois at Chicago, Chicago, IL 60612-7213, USA
*These authors have contributed equally to this work
Anxun Wang, email: [email protected]
Keywords: tongue squamous cell carcinoma, pyruvate kinase M2, metastasis, manganese superoxide dismutase, miR-138
Received: December 23, 2016 Accepted: June 20, 2017 Published: July 17, 2017
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.
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