Yang Xinghai, Li Lei, Huang Quan, Xu Wei, Cai Xiaopan, Zhang Jishen, Yan Wangjun, Song Dianwen, Liu Tielong, Zhou Wang, Li Zhenxi, Yang Cheng, Dang Yongyan, Xiao Jianru
Department of Orthopedic Oncology, Changzheng Hospital, The Second Military Medical University 415 Fengyang Road, Shanghai 200003, China.
Shanghai Key Laboratory of Regulatory Biology, Institute of Biomedical Sciences, School of Life Sciences, East China Normal University 500 Dongchuan Road, Shanghai 200241, China.
Am J Cancer Res. 2015 Jan 15;5(2):748-55. eCollection 2015.
Wnt-β-catenin signaling participates in the epithelial-mesenchymal transition (EMT) in a variety of cancers; however, its role in lung cancer induced bone metastasis and the underlying mechanisms remain unclear. Here, we demonstrate that β-catenin, Snail1 and Zeb1 were significantly upregulated in bone metastasis tissues from human and mouse compared with the normal controls. E-cadherin expression is negatively regulated by Zeb1, Snail1 and β-catenin during bone metastasis tissues induced by lung cancer. Knocking down Zeb1 and Snail1 in lung cancer cell lines showed increased E-cadherin mRNA expression and less invasion compared with the original cell lines. In addition, β-catenin knockdown led to the increase of E-cadherin and the decrease of Zeb1 and Snail1, which in turn inhibited the invasive properties of lung cancer. Our results demonstrated that Wnt signaling through Snail1 and Zeb1 regulates bone metastasis in lung cancer.
Wnt-β-连环蛋白信号通路参与多种癌症的上皮-间质转化(EMT);然而,其在肺癌诱导的骨转移中的作用及潜在机制仍不清楚。在此,我们证明,与正常对照相比,β-连环蛋白、Snail1和Zeb1在人和小鼠的骨转移组织中显著上调。在肺癌诱导的骨转移组织中,E-钙黏蛋白的表达受到Zeb1、Snail1和β-连环蛋白的负调控。与原始细胞系相比,在肺癌细胞系中敲低Zeb1和Snail1显示E-钙黏蛋白mRNA表达增加且侵袭减少。此外,β-连环蛋白敲低导致E-钙黏蛋白增加以及Zeb1和Snail1减少,进而抑制肺癌的侵袭特性。我们的结果表明,通过Snail1和Zeb1的Wnt信号通路调节肺癌的骨转移。