Oncotarget

Research Papers:

PDZ binding kinase, regulated by FoxM1, enhances malignant phenotype via activation of β-Catenin signaling in hepatocellular carcinoma

Yu-Feng Yang, Ying-Hua Pan, Yun Cao, Jia Fu, Xia Yang, Mei-Fang Zhang _ and Qiu-Hong Tian

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Oncotarget. 2017; 8:47195-47205. https://doi.org/10.18632/oncotarget.17587

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Abstract

Yu-Feng Yang1,*, Ying-Hua Pan2,*, Yun Cao3,*, Jia Fu3, Xia Yang3, Mei-Fang Zhang3 and Qiu-Hong Tian4

1Department of Pathology, Dongguan Third People's Hospital, Dongguan, China

2Department of Rheumatology and Immunology, The Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China

3Department of Pathology, Sun Yat-Sen University Cancer Center, Guangzhou, China

4Department of Oncology, First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, China

*These authors contributed equally to this work

Correspondence to:

Mei-Fang Zhang, email: zhangmf@sysucc.org.cn

Qiu-Hong Tian, email: tianqiuhong@hotmail.com

Keywords: PBK, FoxM1, β-Catenin, HCC

Received: January 13, 2017     Accepted: April 17, 2017     Published: May 03, 2017

ABSTRACT

Deregulation of serine/threonine kinase contributes to the development and progression of human diseases. PDZ-binding kinase (PBK) has been implicated in the malignant process of cancers, but its role and clinical significance in hepatocellular carcinoma (HCC) remains unclear. Here we show that PBK expression is increased and associated with larger tumor size, presence of vascular invasion, lymph node metastasis and poor overall and disease-free survivals in two independent cohorts of 879 patients with HCC. In vitro and in vivo data demonstrate PBK exerts oncogenic functions in HCC via activation of β-Catenin signaling pathway. The inhibition of β-Catenin by siRNAs or XAV-939 significantly attenuates PBK-mediated malignant phenotypes. PBK is further identified as a downstream effector of FoxM1. In clinical samples, PBK expression is positively correlated with the expression of FoxM1 and nuclear β-Catenin. Collectively, these findings suggest PBK functions as an oncogene in HCC and the newly identified FoxM1/PBK/β-Catenin axis serves as a promising prognostic factor as well as therapeutic intervention for HCC.


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