Open AccessPDZ binding kinase (PBK) is a theranostic target for nasopharyngeal carcinoma: driving tumor growth via ROS signaling and correlating with patient survival
Author(s) -
Meng Yao Wang,
Zijia Lin,
Yun Cao,
Lichun Zheng,
Peng Li,
Rui Sun,
Di Meng,
Ping Xie,
Jun Yang,
Li Cao,
Liang Xu,
Bi Huang,
Chao Nan Qian
Publication year - 2016
Publication title -
oncotarget
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.373
H-Index - 127
ISSN - 1949-2553
DOI - 10.18632/oncotarget.8445
Subject(s) - pdz domain , nasopharyngeal carcinoma , cancer research , medicine , signal transduction , kinase , biology , microbiology and biotechnology , radiation therapy
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.