Wang Min, Ren Dong, Guo Wei, Huang Shuai, Wang Zeyu, Li Qiji, Du Hong, Song Libing, Peng Xinsheng
Department of Orthopaedic Surgery, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong 510080, P.R. China.
Department of Pathology, The First People's Hospital of Guangzhou City, Guangzhou, Guangdong 510180, P.R. China.
Int J Oncol. 2016 Feb;48(2):595-606. doi: 10.3892/ijo.2015.3270. Epub 2015 Nov 26.
N-cadherin has been reported to be upregulated and associated with metastasis and poor prognosis in prostate cancer patients, however the underlying mechanism still remains puzzling. In the present study, we found that upregulation of N-cadherin enhanced, while downregulation of N-cadherin impaired the invasion, migration, and epithelial to mesenchymal transition (EMT) of prostate cancer (PCa) cells. Overexpression of N-cadherin increased the efficiency of colony and tumor spheroid formation and the stemness factor expression (including c-Myc, Klf4, Sox2 and Oct4), and vice versa. Furthermore, microarray analysis and western blot analysis mechanistically proved that N-cadherin activated ErbB signaling pathway by upregulating the expression of Grb2, pShc and pERK1/2. Importantly, the regulation of N-cadherin on EMT and stemness was counteracted by lapatinib, a specific ErbB signaling pathway inhibitor. Collectively, these findings demonstrate that N-cadherin regulates EMT and stemness of PCa cells via activating ErbB signaling pathway, which indicates the pivotal role of N-cadherin/ErbB axis in the metastasis of prostate cancer.
据报道，N-钙黏蛋白在前列腺癌患者中上调，并与转移和不良预后相关，但其潜在机制仍不清楚。在本研究中，我们发现N-钙黏蛋白的上调增强了前列腺癌细胞的侵袭、迁移和上皮-间质转化（EMT），而N-钙黏蛋白的下调则损害了这些过程。N-钙黏蛋白的过表达提高了集落和肿瘤球形成的效率以及干性因子的表达（包括c-Myc、Klf4、Sox2和Oct4），反之亦然。此外，基因芯片分析和蛋白质印迹分析从机制上证明，N-钙黏蛋白通过上调Grb2、pShc和pERK1/2的表达激活ErbB信号通路。重要的是，拉帕替尼（一种特异性ErbB信号通路抑制剂）抵消了N-钙黏蛋白对EMT和干性的调节作用。总的来说，这些发现表明N-钙黏蛋白通过激活ErbB信号通路调节前列腺癌细胞的EMT和干性，这表明N-钙黏蛋白/ErbB轴在前列腺癌转移中起关键作用。
