Transforming growth factor-β1 induces epithelial-to-mesenchymal transition in human lung cancer cells via PI3K/Akt and MEK/Erk1/2 signaling pathways

被引:218
作者
Chen, Xiao-Feng [1 ]
Zhang, Hui-Jun [1 ,2 ]
Wang, Hai-Bing [1 ]
Zhu, Jun [4 ]
Zhou, Wen-Yong [1 ]
Zhang, Hui [1 ]
Zhao, Ming-Chuan [1 ]
Su, Jin-Mei [3 ]
Gao, Wen [1 ]
Zhang, Lei [1 ]
Fei, Ke [2 ]
Zhang, Hong-Tao [5 ]
Wang, He-Yong [6 ]
机构
[1] Tongji Univ, Dept Thorac Surgury, Shanghai Pulm Hosp, Shanghai 200092, Peoples R China
[2] Tongji Univ, Dept Thorac Surgury, Peoples Hosp 10, Shanghai 200092, Peoples R China
[3] Tongji Univ, Dept Integrated Chinese Med & Western Med, Shanghai Pulm Hosp, Shanghai 200092, Peoples R China
[4] Forth Peoples Hosp Wuxi, Dept Thorac Surgury, Wuxi, Jiangsu, Peoples R China
[5] Soochow Univ, Lab Canc Mol Genet, Coll Med, Suzhou, Peoples R China
[6] Tongji Univ, Cent Lab, Shanghai Pulm Hosp, Shanghai 200092, Peoples R China
基金
美国国家科学基金会;
关键词
TGF-beta; 1; EMT; A549; PI3K/Akt; MAPK/Erk1/2; GROWTH-FACTOR-BETA; DEPENDENT MECHANISM; TUMOR PROGRESSION; BREAST-CANCER; METASTASIS; TRANSDIFFERENTIATION; TGF-BETA-1; RAS; OSTEOPONTIN; DISSECTION;
D O I
10.1007/s11033-011-1128-0
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
070307 [化学生物学]; 071010 [生物化学与分子生物学];
摘要
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.
引用
收藏
页码:3549 / 3556
页数:8
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