PKM2 regulates proliferation and apoptosis through the Hippo pathway in oral tongue squamous cell carcinoma

Jia Luo; Lei Zhang; Lijuan Guo; Sen Yang

doi:10.3892/ol.2021.12722

PKM2 regulates proliferation and apoptosis through the Hippo pathway in oral tongue squamous cell carcinoma

Oncol Lett. 2021 Jun;21(6):461. doi: 10.3892/ol.2021.12722. Epub 2021 Apr 11.

Authors

Jia Luo¹, Lei Zhang², Lijuan Guo³, Sen Yang¹

Affiliations

¹ Department of Oral and Maxillofacial Surgery, Suining Central Hospital, Suining, Sichuan 629000, P.R. China.
² Department of Endodontics, The First Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang 150001, P.R. China.
³ Medical Beauty Department, Suining Central Hospital, Suining, Sichuan 629000, P.R. China.

Abstract

Oral tongue squamous cell carcinoma (OTSCC) is a highly malignant type of tumor. The 5-year survival rate of patients with advanced tongue squamous cell carcinoma is only ~50%. Pyruvate kinase M2 (PKM2) is the key rate-limiting enzyme of glycolysis, maintaining the Warburg effect in tumor cells. The present study aimed to investigate the relationship between PKM2 expression and the poor prognosis of patients with OTSCC and to determine oral squamous carcinoma tumor cell proliferation and apoptosis. Reverse transcription-quantitative (RT-q) PCR, western blotting and immunohistochemistry were used to analyze the expression levels of PKM2 in OTSCC, and the clinicopathological characteristics and prognosis of patients with OTSCC were further analyzed by statistical analysis. The results from RT-qPCR and immunohistochemistry demonstrated that PKM2 was upregulated in OTSCC tissues and highly expressed in advanced stage OTSCC tissues compared with paired adjacent tissues and lower stage OTSCC tissues. Patients with OTSCC and high PKM2 expression had shorter overall survival (OS) compared with those with low PKM2 expression. Furthermore, high expression of PKM2 was significantly associated with Tumor-Node-Metastasis (TNM) stage. TNM stage and PKM2 expression were independent predictive factors for OS in patients with OTSCC. In addition, PKM2 knockdown inhibited the proliferation and increased the apoptosis of oral squamous carcinoma tumor cells. Furthermore, PKM2 knockdown could regulate the expression of cell cycle and apoptosis-related proteins by activating Hippo signaling pathway, as confirmed by the decreased expression of yes-associated protein 1 (YAP), Bcl-2 and Ki-67 and the increased expression of large tumor suppressor kinase 1, phosphorylated YAP and Bax. Taken together, the findings from this study demonstrated that PKM2 may be considered as a potential target for the diagnosis and treatment of OTSCC.

Keywords: Hippo pathway; apoptosis; oral tongue squamous cell carcinoma; proliferation; pyruvate kinase M2.

Grants and funding

This work was supported by the Key Research and Development Projects of Sichuan Science and Technology Department (grant no. 2018FZ0113), the China Stomatological Association Western Medicine Stomatology Clinical Research Fund Project (grant no. CSA-W2016-01), the Sichuan Science and Technology Support Program (grant no. 2014SZ0038) and the Sichuan Provincial Primary Health Service Development Research Fund (grant no. SWFZ20-C-086).