Research Papers:

PDZ binding kinase (PBK) is a theranostic target for nasopharyngeal carcinoma: driving tumor growth via ROS signaling and correlating with patient survival

Meng-Yao Wang _, Zhi-Rui Lin, Yun Cao, Li-Sheng Zheng, Li-Xia Peng, Rui Sun, Dong-Fang Meng, Ping Xie, Jun-Ping Yang, Li Cao, Liang Xu, Bi-Jun Huang and Chao-Nan Qian

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Oncotarget. 2016; 7:26604-26616. https://doi.org/10.18632/oncotarget.8445

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Meng-Yao Wang1,*, Zhi-Rui Lin1,3,*, Yun Cao4, Li-Sheng Zheng1, Li-Xia Peng1, Rui Sun2, Dong-Fang Meng1, Ping Xie1, Jun-Ping Yang1, Li Cao5, Liang Xu1, Bi-Jun Huang1, Chao-Nan Qian1,2

1State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, Guangdong, China

2Department of Nasopharyngeal Carcinoma, Sun Yat-sen University Cancer Center, Guangzhou, Guangdong, China

3Key Laboratory of Medical Reprogramming Technology, Shenzhen Second People’s Hospital, the First Affiliated Hospital of Shenzhen University, Shenzhen, China

4Department of Pathology, Sun Yat-sen University Cancer Center, Guangzhou, Guangdong, China

5Department of Pharmacy, Sun Yat-sen University Cancer Center, Guangzhou, Guangdong, China

*These authors contributed equally to this work

Correspondence to:

Chao-Nan Qian, e-mail: [email protected]

Keywords: PBK/TOPK, nasopharyngeal carcinoma, ROS, JNK/P38 pathway

Received: January 02, 2016    Accepted: February 19, 2016    Published: March 28, 2016


Nasopharyngeal carcinoma (NPC) is well known as one of the most common malignancies in southern China and Southeast Asia. However, the mechanisms underlying NPC progression remain poorly understood. Herein, through overlapping the differentially expressed genes from 3 microarray data sets with the human kinome, we identified PBK, a serine-threonine kinase, is highly upregulated and has not been intensively investigated in NPC. PBK was required for malignant phenotypes of NPC, as PBK depletion by RNAi and inhibition by specific inhibitor HI-TOPK-032 obviously reduced cell proliferation and xenograft tumor growth in mice. Moreover, we determined that targeting PBK could accelerate apoptosis by inducing ROS that activates JNK/p38 signaling pathway. In NPC patients, elevated PBK expression in primary tumor positively correlated to clinical severity such as advanced T stage, high death risk and disease progression, and it could serve as an unfavorable independent indicator of overall survival and disease-free survival. Altogether, our results indicate that PBK is a novel significant regulator of NPC progression and a potential therapeutic target for NPC patients.

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