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Norepinephrine induced epithelial–mesenchymal transition in HT-29 and A549 cells in vitro

  • Original Article – Cancer Research
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Abstract

Purpose

Norepinephrine (NE) has been implicated in epithelial–mesenchymal transition (EMT) of cancer cells. However, the underlying mechanism is poorly understood. The goal of this study was to explore the effect of NE on cancer cell EMT and to investigate the potential mechanism.

Methods

HT-29 and A549 cells were treated with NE, β-adrenergic receptor (β-AR) antagonist (propranolol) or inhibitor of transforming growth factor-β (TGF-β) receptor type I kinase (Ly2157299). Morphology of cells was observed with optical and electron microscope and immunofluorescence staining. Cellular migration and invasion were tested with transwell migration assay and Matrigel invasion assay, respectively. TGF-β1 and cyclic adenosine monophosphate (cAMP) were quantified. EMT markers and signaling pathway were measured by RT-PCR and western blot.

Results

NE stimulated TGF-β1 secretion and intracellular cAMP synthesis, induced morphological alterations in HT-29 and A549 cells, and enhanced their ability of migration and invasion. EMT markers induction was observed in NE-treated cancer cells. The effect of NE could be inhibited by propranolol or Ly2157299. β-AR/TGF-β1 signaling/p-Smad3/Snail and β-AR/TGF-β1 signaling/HIF-1α/Snail were two signaling pathways.

Conclusion

These findings demonstrated that TGF-β1 signaling pathway was a significant factor of NE-induced cancer cells EMT. The data also suggested that psychological stress might be a risk factor which enhances the ability of migration or invasion of cancer cells.

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Acknowledgments

This study was supported by the National Natural Science Foundation of China (81172202). We thank Lei Deng, M.D. and Mr Di Luo for the English editing.

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    Authors and Affiliations

    1. Department of Medical Oncology, Cancer Center, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, No. 37 Guo-Xue Xiang, Chengdu, 610041, Sichuan, People’s Republic of China

      Jie Zhang, Yao-tiao Deng, Jie Liu, Yu-qing Wang, Ting-wu Yi, Bo-yan Huang, Sha-sha He, Bo Zheng & Yu Jiang

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    1. Jie Zhang
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    Jie Zhang and Yao-tiao Deng have contributed equally to this work.

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    Zhang, J., Deng, Yt., Liu, J. et al. Norepinephrine induced epithelial–mesenchymal transition in HT-29 and A549 cells in vitro. J Cancer Res Clin Oncol 142, 423–435 (2016). https://doi.org/10.1007/s00432-015-2044-9

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