Transforming growth factor-β1 induces epithelial-to-mesenchymal transition in human lung cancer cells via PI3K/Akt and MEK/Erk1/2 signaling pathways
Transforming growth factor-β1 induces epithelial-to-mesenchymal transition in human lung cancer cells via PI3K/Akt and MEK/Erk1/2 signaling pathways
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DOI：
10.1007/s11033-011-1128-0
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发表时间：
2012-04-01
影响因子：
2.8
通讯作者：
Wang, He-Yong
中科院分区：
文献类型：
--
作者：
Chen, Xiao-Feng;Zhang, Hui-Jun;Wang, He-Yong
肿瘤细胞的转移与上皮细胞向间充质细胞的转变(EMT)有关，EMT是上皮细胞失去其极性并获得新的间质特征的过程。已有报道由转化生长因子-β1(TGF-β1)诱导EMT，但其机制尚不清楚。本研究旨在探讨PI3K/Akt和MAPK/ERK1/2信号通路是否参与人肺癌A549细胞的EMT。结果表明，经转化生长因子-β1作用48h后，A549细胞呈成纤维细胞样变，上皮标志物E-钙粘附素缺失，间质标志物Vimentin和FN表达增强。此外，转化生长因子-β1诱导的EMT在48h后伴随着细胞迁移增加和Akt和ERK1/2磷酸化的变化。此外，PI3K抑制剂LY294002和MEK1/2抑制剂U0126逆转了A549细胞的EMT，提示在转化生长因子-β1的刺激下，A549细胞发生了向间充质细胞的转换，PI3K/Akt和MAPK/ERK1/2信号通路参与了调控转化生长因子-β1诱导的A549细胞的EMT。
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-beta 1 (TGF-beta 1), 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-beta 1 for 48 h, A549 cells displayed more fibroblast-like shape, lost epithelial marker E-cadherin and increased mesenchymal markers Vimentin and Fibronectin. Moreover, TGF-beta 1-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-beta 1 undergo a switch into mesenchymal cells and PI3K/Akt and MAPK/Erk1/2 signaling pathways serve to regulate TGF-beta 1-induced EMT of A549 cells.