Overexpression of pyruvate kinase M2 associates with aggressive clinicopathological features and unfavorable prognosis in oral squamous cell carcinoma

被引：38

作者：

Wang, Yanling ^{[1
,2
]}

Zhang, Xiaomin ^{[1
,2
]}

Zhang, Yuchao ^{[1
,2
]}

Zhu, Yuming ^{[1
]}

Yuan, Chunping ^{[1
]}

Qi, Bin ^{[3
]}

Zhang, Wei ^{[3
]}

Wang, Dongmiao ^{[1
]}

Ding, Xu ^{[1
]}

Wu, Heming ^{[1
,2
]}

Cheng, Jie ^{[1
,2
]}

机构：

[1] Nanjing Med Univ, Affiliated Stomatol Hosp, Jiangsu Key Lab Oral Dis, Nanjing, Jiangsu, Peoples R China

[2] Nanjing Med Univ, Affiliated Stomatol Hosp, Dept Oral & Maxillofacial Surg, Nanjing, Jiangsu, Peoples R China

[3] Nanjing Med Univ, Affiliated Stomatol Hosp, Dept Oral Pathol, Nanjing, Jiangsu, Peoples R China

来源：

CANCER BIOLOGY & THERAPY | 2015年 / 16卷 / 06期

基金：

中国博士后科学基金;

关键词：

aerobic glycolysis; oral squamous cell carcinoma; PKM2; pyruvate kinase M2; Warburg effect; NUCLEAR TRANSLOCATION; TONGUE; PKM2; INHIBITION; GLYCOLYSIS; EXPRESSION;

D O I：

10.1080/15384047.2015.1030551

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

Abnormal glucose metabolism mediated by pyruvate kinase M2 (PKM2) fuels cancer overgrowth and propagation. However, its expression and oncogenic roles in in oral squamous cell carcinoma (OSCC) remains incompletely known. Here, we aimed to investigate the expression of PKM2, its prognostic values and oncogenic functions using 7,12-dimethyl-1,2-bezan-tracene (DMBA)-induced hamster buccal pouch SCC model, primary OSCC specimens as well as in vitro cellular assays. We found that in DMBA-induced OSCC model, negative PKM2 expression was commonly observed in normal epithelial, while more PKM2 abundance was detected in hyperplasia, dysplasia and SCC. Overexpression of PKM2 in a major fraction of OSCC significantly associated with tumor size (P = 0.027), cervical node metastasis (P = 0.004) and clinical stages (P = 0.000). Patients with increased PKM2 had remarkably reduced overall and disease-free survival. Multivariate survival analysis further revealed that PKM served as a critical independent prognostic factor for patients' overall survival. Furthermore, impaired cell proliferation and migration, and reduced apoptosis were detected upon PKM2 knockdown in HN4 and HN12 cells. Taken together, our findings reveal that PKM2 is critically involved in OSCC initiation and progression probably by promoting cell proliferation and migration as well as reducing apoptosis. Its overexpression correlates with aggressive clinicopathological features and poor patients' outcome.

引用

页码：839 / 845

页数：7