CUL4B promotes bladder cancer metastasis and induces epithelial-to-mesenchymal transition by activating the Wnt/β-catenin signaling pathway.
CUL4B promotes bladder cancer metastasis and induces epithelial-to-mesenchymal transition by activating the Wnt/β-catenin signaling pathway.
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CUL4B通过激活Wnt/β-catenin信号通路促进膀胱癌转移并诱导上皮间质转化
DOI：
10.18632/oncotarget.20455
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发表时间：
2017-09-29
期刊：
影响因子：
--
通讯作者：
Zhang N
中科院分区：
文献类型：
--
作者：
Mao XW;Xiao JQ;Xu G;Li ZY;Wu HF;Li Y;Zheng YC;Zhang N
Cullin 4B(CUL4B)的高表达与几种癌症的进展有关。本研究旨在探讨CUL4B在膀胱癌转移和上皮间充质转化过程中的作用及其与Wnt/β-catenin信号通路的关系。收集124例胆囊癌患者的癌组织及癌旁正常组织。采用实时定量聚合酶链式反应和Western blotting检测Wnt/β-catenin信号通路相关蛋白和EMT标志物的表达。用四甲基偶氮唑盐比色法和Transwell法检测细胞的增殖、迁移和侵袭能力。用对照、siRNA干扰控制(siRNA-NC)、si-CUL4B和CUL4B或Wnt抑制因子1(WIF-1)高表达载体分别转染BC 5637细胞。与癌旁正常组织相比，癌组织中CUL4B基因和蛋白的表达水平均升高。CUL4B表达与E-钙粘蛋白表达呈负相关，与N-钙粘蛋白、Vimentin表达呈正相关。与对照组相比，si-CUL4B组和WIF-1组β-catenin、cyClinD1、c-myc、MMP7和EMT标志物水平降低，而磷酸化GSK3WIF-1组β-Ser9和E-钙粘素水平升高。此外，细胞的增殖、迁移和侵袭能力也有所增强。增加CUL4B的表达则有相反的作用。这些结果提示CUL4B通过激活Wnt/β-catenin信号通路诱导内皮细胞转化，促进BC的转移。
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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影响因子：
6.2
作者：
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作者：
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影响因子：
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作者：
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