title: Norepinephrine induced epithelial-mesenchymal transition in HT-29 and A549 cells in vitro.
abstract: OBJECTIVE
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: 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.
authors.forename: Jie
authors.initials: J
authors.lastname: Zhang
authors.affiliation: 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.
authors.forename: Yao-tiao
authors.initials: YT
authors.lastname: Deng
authors.affiliation: 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.
authors.forename: Jie
authors.initials: J
authors.lastname: Liu
authors.affiliation: 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.
authors.forename: Yu-qing
authors.initials: YQ
authors.lastname: Wang
authors.affiliation: 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.
authors.forename: Ting-wu
authors.initials: TW
authors.lastname: Yi
authors.affiliation: 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.
authors.forename: Bo-yan
authors.initials: BY
authors.lastname: Huang
authors.affiliation: 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.
authors.forename: Sha-sha
authors.initials: SS
authors.lastname: He
authors.affiliation: 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.
authors.forename: Bo
authors.initials: B
authors.lastname: Zheng
authors.affiliation: 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. jiangyu1973@hotmail.com.
authors.forename: Yu
authors.initials: Y
authors.lastname: Jiang
mesh_terms: D000319:Adrenergic beta-Antagonists / Q000494:pharmacology; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D015179:Colorectal Neoplasms / Q000378:metabolism / Q000473:pathology; D000242:Cyclic AMP / Q000378:metabolism; D058750:Epithelial-Mesenchymal Transition / Q000187:drug effects*; D019073:HT29 Cells; D006801:Humans; D008175:Lung Neoplasms / Q000378:metabolism / Q000473:pathology; D009638:Norepinephrine / Q000494:pharmacology*; D011433:Propranolol / Q000494:pharmacology; D011720:Pyrazoles / Q000494:pharmacology; D011804:Quinolines / Q000494:pharmacology; D053773:Transforming Growth Factor beta1 / Q000037:antagonists & inhibitors / Q000378:metabolism
chemical_list: D000319:Adrenergic beta-Antagonists; D011720:Pyrazoles; D011804:Quinolines; D053773:Transforming Growth Factor beta1; C557799:LY-2157299; D011433:Propranolol; D000242:Cyclic AMP; D009638:Norepinephrine
keywords: Adrenergic receptor; Chronic stress; Epithelial–mesenchymal transition; Norepinephrine; Transforming growth factor-β1