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.
PDZ binding kinase (PBK) is a theranostic target for nasopharyngeal carcinoma: driving tumor growth via ROS signaling and correlating with patient survival.
PDZ 结合激酶 (PBK) 是鼻咽癌的治疗诊断靶点:通过 ROS 信号传导驱动肿瘤生长,并与患者生存率相关
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作者:Wang Meng-Yao, Lin Zhi-Rui, Cao Yun, Zheng Li-Sheng, Peng Li-Xia, Sun Rui, Meng Dong-Fang, Xie Ping, Yang Jun-Ping, Cao Li, Xu Liang, Huang Bi-Jun, Qian Chao-Nan
| 期刊: | Oncotarget | 影响因子: | 0.000 |
| 时间: | 2016 | 起止号: | 2016 May 3; 7(18):26604-16 |
| doi: | 10.18632/oncotarget.8445 | 研究方向: | 信号转导、肿瘤 |
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