N-cadherin promotes epithelial-mesenchymal transition and cancer stem cell-like traits via ErbB signaling in prostate cancer cells
N-cadherin promotes epithelial-mesenchymal transition and cancer stem cell-like traits via ErbB signaling in prostate cancer cells
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N-钙粘蛋白通过前列腺癌细胞中的 ErbB 信号传导促进上皮间质转化和癌症干细胞样特征
DOI：
10.3892/ijo.2015.3270
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发表时间：
2016-02-01
影响因子：
5.2
通讯作者：
Peng, Xinsheng
中科院分区：
文献类型：
--
作者：
Wang, Min;Ren, Dong;Peng, Xinsheng
据报道，n -钙粘蛋白在前列腺癌患者中表达上调并与转移和预后不良相关，但其潜在机制尚不清楚。在本研究中，我们发现N-cadherin的上调增强了前列腺癌（PCa）细胞的侵袭、迁移和上皮向间质转化（EMT），而N-cadherin的下调则削弱了前列腺癌（PCa）细胞的侵袭、迁移和上皮向间质转化（EMT）。过表达N-cadherin可提高集落和肿瘤球体的形成效率以及干细胞因子（包括c-Myc、Klf4、Sox2和Oct4）的表达，反之亦然。此外，微阵列分析和western blot分析机制证实N-cadherin通过上调Grb2、pShc和pERK1/2的表达激活ErbB信号通路。重要的是，N-cadherin对EMT和干性的调节被拉帕替尼（一种特异性ErbB信号通路抑制剂）抵消。综上所述，这些发现表明N-cadherin通过激活ErbB信号通路调节前列腺癌细胞的EMT和干性，提示N-cadherin/ErbB轴在前列腺癌转移中的关键作用。
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.