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CUL4B promotes bladder cancer metastasis and induces epithelial-to-mesenchymal transition by activating the Wnt/β-catenin signaling pathway

Xia-Wa Mao, Jia-Quan Xiao, Gang Xu, Zhong-Yi Li, Hui-Feng Wu, Yi Li, Yi-Chun Zheng and Nan Zhang _

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Oncotarget. 2017; 8:77241-77253. https://doi.org/10.18632/oncotarget.20455

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Abstract

Xia-Wa Mao1, Jia-Quan Xiao1, Gang Xu1, Zhong-Yi Li1, Hui-Feng Wu1, Yi Li1, Yi-Chun Zheng1 and Nan Zhang1

1Department of Urology, The Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou 310009, P.R. China

Correspondence to:

Nan Zhang, email: [email protected]

Keywords: CUL4B, Wnt/β-catenin signaling pathway, bladder cancer, epithelial-to-mesenchymal transition, proliferation

Received: September 20, 2016     Accepted: July 11, 2017      Published: August 24, 2017

ABSTRACT

Increased expression of cullin 4B (CUL4B) is linked to progression in several cancers. This study aims to explore the effects of CUL4B on bladder cancer (BC) metastasis and epithelial-to-mesenchymal transition (EMT) and potential correlation to the Wnt/β-catenin signaling pathway. We collected BC tissues and adjacent normal tissues from 124 BC patients. Quantitative real-time polymerase chain reaction (qRT-PCR) and western blotting were employed in order to detect the expression of Wnt/β-catenin signaling pathway-related proteins and EMT markers. MTT and Transwell assays were used in order to measure cell proliferation, migration, and invasion. BC 5637 cells were transfected with control, siRNA scramble control (siRNA-NC), si-CUL4B, and CUL4B or Wnt inhibitory factor 1 (WIF-1) overexpression constructs. Levels of CUL4B mRNA and protein were increased in BC tissues in comparison with the adjacent normal tissues. CUL4B expression was negatively correlated with the expression of E-cadherin and positively correlated to the expression of N-cadherin and Vimentin. Compared to the control group, levels of β-catenin, cyclinD1, c-myc, MMP7, and EMT markers were reduced, whereas phosphorylated GSK3βSer9 and E-cadherin levels were increased in the si-CUL4B and WIF-1 groups. In addition, cell proliferation, migration, and invasion abilities were also increased. Increasing CUL4B expression had the opposite effect. These findings suggest that CUL4B induces EMT and promotes metastasis of BC by activating the Wnt/β-catenin signaling pathway.


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