title: Overexpression of pyruvate kinase M2 associates with aggressive clinicopathological features and unfavorable prognosis in oral squamous cell carcinoma.
abstract: 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.
authors.affiliation: a Jiangsu Key Laboratory of Oral Disease; Affiliated Stomatological Hospital; Nanjing Medical University ; Nanjing , PR China.
authors.forename: Yanling
authors.initials: Y
authors.lastname: Wang
authors.forename: Xiaomin
authors.initials: X
authors.lastname: Zhang
authors.forename: Yuchao
authors.initials: Y
authors.lastname: Zhang
authors.forename: Yuming
authors.initials: Y
authors.lastname: Zhu
authors.forename: Chunping
authors.initials: C
authors.lastname: Yuan
authors.forename: Bin
authors.initials: B
authors.lastname: Qi
authors.forename: Wei
authors.initials: W
authors.lastname: Zhang
authors.forename: Dongmiao
authors.initials: D
authors.lastname: Wang
authors.forename: Xu
authors.initials: X
authors.lastname: Ding
authors.forename: Heming
authors.initials: H
authors.lastname: Wu
authors.forename: Jie
authors.initials: J
authors.lastname: Cheng
mesh_terms: D000328:Adult; D000368:Aged; D000818:Animals; D002294:Carcinoma, Squamous Cell / Q000235:genetics* / Q000401:mortality / Q000473:pathology*; D002352:Carrier Proteins / Q000235:genetics* / Q000378:metabolism; D002471:Cell Transformation, Neoplastic / Q000235:genetics; D006224:Cricetinae; D004195:Disease Models, Animal; D018450:Disease Progression; D005260:Female; D015870:Gene Expression; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D008565:Membrane Proteins / Q000235:genetics* / Q000378:metabolism; D008875:Middle Aged; D009062:Mouth Neoplasms / Q000235:genetics* / Q000401:mortality / Q000473:pathology*; D060787:Neoplasm Grading; D009367:Neoplasm Staging; D011379:Prognosis; D013963:Thyroid Hormones / Q000235:genetics* / Q000378:metabolism; D047368:Tumor Burden; D000097810:Thyroid Hormone-Binding Proteins
chemical_list: D002352:Carrier Proteins; D008565:Membrane Proteins; D013963:Thyroid Hormones; D000097810:Thyroid Hormone-Binding Proteins
keywords: PKM2; Warburg effect; aerobic glycolysis; oral squamous cell carcinoma; pyruvate kinase M2