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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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Abstract

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.

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Abbreviations

EGF:

Epidermal growth factor

EMT:

Epithelial-to-mesenchymal transition

FGF:

Fibroblast growth factor

HGF/SF:

Hepatocyte growth factor/scatter factor

TGF-β1:

Transforming growth factor-β1

TβRI:

TGF-β receptors type I

TβRII:

TGF-β receptors type II

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Acknowledgments

This work was supported by Grants from National Science Foundation of China (No. 30872553 and 30800631) and Shanghai Science and Technology Committee (No. 10JC1419200).

Conflict of interest

The authors have no financial conflicts of interest.

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Authors and Affiliations

  1. Department of Thoracic Surgury, Shanghai Pulmonary Hospital, Tongji University, Shanghai, China

    Xiao-Feng Chen, Hui-Jun Zhang, Hai-Bing Wang, Wen-Yong Zhou, Hui Zhang, Ming-Chuan Zhao, Wen Gao & Lei Zhang

  2. Department of Thoracic Surgury, Tenth People’s Hospital of Tongji University, Shanghai, China

    Hui-Jun Zhang & Ke Fei

  3. Department of Integrated Chinese Medicine and Western Medicine, Shanghai Pulmonary Hospital, Tongji University, Shanghai, China

    Jin-Mei Su

  4. Department of Thoracic Surgury, Forth People’s Hospital of Wuxi, Jiangsu, China

    Jun Zhu

  5. Laboratory of Cancer Molecular Genetics, Medical College of Soochow University, Suzhou, China

    Hong-Tao Zhang

  6. Central Laboratory, Shanghai Pulmonary Hospital, Tongji University, Shanghai, China

    He-Yong Wang

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  1. Xiao-Feng Chen
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  2. Hui-Jun Zhang
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Corresponding authors

Correspondence to Xiao-Feng Chen or He-Yong Wang.

Additional information

X.-F. Chen and H.-J. Zhang contributed equally to this study.

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Chen, XF., Zhang, HJ., Wang, HB. et al. Transforming growth factor-β1 induces epithelial-to-mesenchymal transition in human lung cancer cells via PI3K/Akt and MEK/Erk1/2 signaling pathways. Mol Biol Rep 39, 3549–3556 (2012). https://doi.org/10.1007/s11033-011-1128-0

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