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CUL4B通过激活Wnt/β-连环蛋白信号通路促进膀胱癌转移并诱导上皮-间质转化。

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

作者信息

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

机构信息

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

出版信息

Oncotarget. 2017 Aug 24;8(44):77241-77253. doi: 10.18632/oncotarget.20455. eCollection 2017 Sep 29.

DOI:10.18632/oncotarget.20455
PMID:29100384
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC5652777/
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 GSK3β 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.

摘要

cullin 4B（CUL4B）表达增加与多种癌症的进展相关。本研究旨在探讨CUL4B对膀胱癌（BC）转移和上皮-间质转化（EMT）的影响及其与Wnt/β-连环蛋白信号通路的潜在相关性。我们收集了124例BC患者的BC组织和癌旁正常组织。采用定量实时聚合酶链反应（qRT-PCR）和蛋白质印迹法检测Wnt/β-连环蛋白信号通路相关蛋白和EMT标志物的表达。采用MTT法和Transwell实验检测细胞增殖、迁移和侵袭能力。用对照、小干扰RNA（siRNA）乱序对照（siRNA-NC）、si-CUL4B以及CUL4B或Wnt抑制因子1（WIF-1）过表达构建体转染BC 5637细胞。与癌旁正常组织相比，BC组织中CUL4B mRNA和蛋白水平升高。CUL4B表达与E-钙黏蛋白表达呈负相关，与N-钙黏蛋白和波形蛋白表达呈正相关。与对照组相比，si-CUL4B组和WIF-1组中β-连环蛋白、细胞周期蛋白D1、c-myc、基质金属蛋白酶7（MMP7）和EMT标志物水平降低，而磷酸化糖原合成酶激酶3β（GSK3β）和E-钙黏蛋白水平升高。此外，细胞增殖、迁移和侵袭能力也增强。增加CUL4B表达则产生相反的效果。这些发现表明，CUL4B通过激活Wnt/β-连环蛋白信号通路诱导EMT并促进BC转移。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b6de/5652777/71bc0a87d222/oncotarget-08-77241-g010.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b6de/5652777/8ee7187a83d1/oncotarget-08-77241-g001.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b6de/5652777/c6a0cebf5b88/oncotarget-08-77241-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b6de/5652777/fba1a5785cfe/oncotarget-08-77241-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b6de/5652777/b81706552925/oncotarget-08-77241-g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b6de/5652777/c38f56e97ee0/oncotarget-08-77241-g009.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b6de/5652777/71bc0a87d222/oncotarget-08-77241-g010.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b6de/5652777/8ee7187a83d1/oncotarget-08-77241-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b6de/5652777/22dea069a565/oncotarget-08-77241-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b6de/5652777/ef6169b9df26/oncotarget-08-77241-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b6de/5652777/1ded50013cdd/oncotarget-08-77241-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b6de/5652777/65fee6cf0719/oncotarget-08-77241-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b6de/5652777/c6a0cebf5b88/oncotarget-08-77241-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b6de/5652777/fba1a5785cfe/oncotarget-08-77241-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b6de/5652777/b81706552925/oncotarget-08-77241-g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b6de/5652777/c38f56e97ee0/oncotarget-08-77241-g009.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b6de/5652777/71bc0a87d222/oncotarget-08-77241-g010.jpg

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