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

Oncotarget
Yu-Feng YangQiu-Hong Tian

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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Citations

Aug 28, 2017·Virchows Archiv : an International Journal of Pathology·Achim H BellDiana Bell
Mar 9, 2018·The Journal of Clinical Investigation·Amber W WangKlaus H Kaestner
Feb 19, 2020·Expert Opinion on Therapeutic Targets·Soheila Borhani, Andrei L Gartel
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Feb 28, 2021·Virchows Archiv : an International Journal of Pathology·Aya Nagano-MatsuoSatoru Takahashi
Mar 28, 2021·Journal of Translational Medicine·Mingxing XuYunbiao Ling

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Methods Mentioned

BETA
transfection
PCR

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