title: Nicotine promotes cell migration through alpha7 nicotinic acetylcholine receptor in gastric cancer cells.
abstract: BACKGROUND
  The objective was to study the mechanism of nicotine-enhanced migration of gastric cancer cells. Long-term cigarette smoking increases the risk of gastric cancer mortality. Tobacco-specific mitogen, nicotine, was reported to correlate with cancer progression on gastric cancer. Since metastasis is the major cause of cancer death, the influence of nicotine on the migration of gastric cancer cells remains to be determined.
  
  
  METHODS
  The influence of nicotine on migration of gastric cancer cells was evaluated by transwell assay and wound-healing migration assay. Receptor-mediated migration was studied by both inhibitor and small interfering RNA.
  
  
  RESULTS
  Alpha7 nicotinic acetylcholine receptor, alpha7-nAChR, was identified in gastric cancer cell lines, AGS cells. Nicotine enhanced AGS cell migration in transwell assay and wound-healing migration assay in a dose-dependent manner. We used inhibitor and siRNA to demonstrate that alpha7-nAChR mediated nicotine-enhanced gastric cancer cell migration through downregulation E-cadherin and upregulation ZEB-1 and snail.
  
  
  CONCLUSIONS
  Tobacco-specific mitogen, nicotine, enhanced gastric cancer metastasis through alpha7-nAChR and suppression of E-cadherin level-one of the hallmarks of epithelial to mesenchymal transition. Therefore, patients with gastric cancer should avoid smoking.
authors.affiliation: Division of General Surgery, Department of Surgery, Taipei Medical University Hospital, Taipei, Taiwan.
authors.forename: Yung-Chang
authors.initials: YC
authors.lastname: Lien
authors.forename: Weu
authors.initials: W
authors.lastname: Wang
authors.forename: Li-Jen
authors.initials: LJ
authors.lastname: Kuo
authors.forename: Jun-Jen
authors.initials: JJ
authors.lastname: Liu
authors.forename: Po-Li
authors.initials: PL
authors.lastname: Wei
authors.forename: Yuan-Soon
authors.initials: YS
authors.lastname: Ho
authors.forename: Wen-Chien
authors.initials: WC
authors.lastname: Ting
authors.forename: Chih-Hsiung
authors.initials: CH
authors.lastname: Wu
authors.forename: Yu-Jia
authors.initials: YJ
authors.lastname: Chang
mesh_terms: D015153:Blotting, Western; D002448:Cell Adhesion / Q000187:drug effects; D002454:Cell Differentiation / Q000187:drug effects; D002465:Cell Movement / Q000187:drug effects*; D049109:Cell Proliferation / Q000187:drug effects; D058750:Epithelial-Mesenchymal Transition / Q000187:drug effects; D006801:Humans; D009538:Nicotine / Q000494:pharmacology*; D018722:Nicotinic Agonists / Q000494:pharmacology*; D012333:RNA, Messenger / Q000235:genetics; D034741:RNA, Small Interfering / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D011978:Receptors, Nicotinic / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D013274:Stomach Neoplasms / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology*; D014407:Tumor Cells, Cultured; D014945:Wound Healing / Q000187:drug effects; D064569:alpha7 Nicotinic Acetylcholine Receptor
chemical_list: C579167:Chrna7 protein, human; D018722:Nicotinic Agonists; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D011978:Receptors, Nicotinic; D064569:alpha7 Nicotinic Acetylcholine Receptor; D009538:Nicotine