Department of Thoracic Surgury, Shanghai Pulmonary Hospital, Tongji University, Shanghai, China.
Mol Biol Rep. 2012 Apr;39(4):3549-56. doi: 10.1007/s11033-011-1128-0. Epub 2011 Jun 29.
Metastasis of tumor cells is associated with epithelial-to-mesenchymal transition (EMT), which is a process whereby epithelial cells lose their polarity and acquire new features of mesenchyme. EMT has been reported to be induced by transforming growth factor-β1 (TGF-β1), but its mechanism remains elusive. In this study, we performed a study to investigate whether PI3K/Akt and MAPK/Erk1/2 signaling pathways involved in EMT in the human lung cancer A549 cells. The results showed that after treated with TGF-β1 for 48 h, A549 cells displayed more fibroblast-like shape, lost epithelial marker E-cadherin and increased mesenchymal markers Vimentin and Fibronectin. Moreover, TGF-β1-induced EMT after 48 h was accompanied by increased of cell migration and change of Akt and Erk1/2 phosphorylation. In addition, EMT was reversed by PI3K inhibitor LY294002 and MEK1/2 inhibitor U0126, which suggested that A549 cells under stimulation of TGF-β1 undergo a switch into mesenchymal cells and PI3K/Akt and MAPK/Erk1/2 signaling pathways serve to regulate TGF-β1-induced EMT of A549 cells.
肿瘤细胞的转移与上皮-间质转化（EMT）有关，这是一个上皮细胞失去极性并获得间质新特征的过程。已经报道转化生长因子-β1（TGF-β1）诱导 EMT，但其机制仍不清楚。在这项研究中，我们研究了 PI3K/Akt 和 MAPK/Erk1/2 信号通路是否参与人肺癌 A549 细胞中的 EMT。结果表明，用 TGF-β1 处理 48 小时后，A549 细胞呈现出更类似成纤维细胞的形态，失去上皮标志物 E-钙黏蛋白，增加间充质标志物波形蛋白和纤维连接蛋白。此外，TGF-β1 在 48 小时后诱导的 EMT 伴随着细胞迁移的增加和 Akt 和 Erk1/2 磷酸化的改变。此外，PI3K 抑制剂 LY294002 和 MEK1/2 抑制剂 U0126 逆转 EMT，这表明 TGF-β1 刺激下的 A549 细胞经历了向间充质细胞的转变，PI3K/Akt 和 MAPK/Erk1/2 信号通路有助于调节 TGF-β1 诱导的 A549 细胞 EMT。
