title: Nicotine enhances colon cancer cell migration by induction of fibronectin.
abstract: BACKGROUND
  Long-term cigarette smoking increases the risk of colorectal cancer mortality. Tobacco's addictive toxin, nicotine, was reported to increase DNA synthesis of colon cancer cells. Because metastasis is the major cause of cancer death, the influence of nicotine on the migration of colon cancer cells remains to be determined.
  
  
  METHODS
  The influence of nicotine on the migration of colon cancer cells was evaluated using transwell assay. Nicotine receptor-mediated migration was studied by using both inhibitors and small interfering RNA (siRNA). The role of COX-2 signal was studied using pharmacological inhibitors. The expression of epithelial mesenchymal transition (EMT) marker and COX-2 signal was evaluated using real-time polymerase chain reaction (PCR).
  
  
  RESULTS
  Nicotine enhanced DLD-1 and SW480 cell migration in a dose-dependent manner. We used inhibitors and siRNA to demonstrate that α7-nAChR mediates nicotine-enhanced colon cancer cell migration and upregulates fibronectin expression, which is involved in nicotine-enhanced migration. Furthermore, COX-2 signal was induced by nicotine treatment and is involved in nicotine-enhanced fibronectin expression.
  
  
  CONCLUSIONS
  Nicotine, tobacco's additive toxin, enhances colon cancer metastasis through α7-nAChR and fibronectin--a mesenchymal marker for epithelial mesenchymal transition. Furthermore, COX-2 signal was involved in the induction of fibronectin. Therefore, smoking may play role in the progression of colon cancer.
authors.affiliation: Division of General Surgery, Department of Surgery, Taipei Medical University Hospital, Taipei, Taiwan. poliwei@hotmail.com
authors.forename: Po-Li
authors.initials: PL
authors.lastname: Wei
authors.forename: Li-Jen
authors.initials: LJ
authors.lastname: Kuo
authors.forename: Ming-Te
authors.initials: MT
authors.lastname: Huang
authors.forename: Wen-Chien
authors.initials: WC
authors.lastname: Ting
authors.forename: Yuan-Soon
authors.initials: YS
authors.lastname: Ho
authors.forename: Weu
authors.initials: W
authors.lastname: Wang
authors.forename: Jane
authors.initials: J
authors.lastname: An
authors.forename: Yu-Jia
authors.initials: YJ
authors.lastname: Chang
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D015153:Blotting, Western; D002465:Cell Movement / Q000187:drug effects*; D003110:Colonic Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology*; D051546:Cyclooxygenase 2 / Q000235:genetics / Q000378:metabolism; D058750:Epithelial-Mesenchymal Transition; D005353:Fibronectins / Q000378:metabolism*; D006801:Humans; D009538:Nicotine / Q000494:pharmacology*; D018722:Nicotinic Agonists / Q000494:pharmacology*; D012333:RNA, Messenger / Q000235:genetics; D034741:RNA, Small Interfering / Q000235:genetics; D011978:Receptors, Nicotinic / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014407:Tumor Cells, Cultured; D064569:alpha7 Nicotinic Acetylcholine Receptor
chemical_list: C579167:Chrna7 protein, human; D005353:Fibronectins; D018722:Nicotinic Agonists; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D011978:Receptors, Nicotinic; D064569:alpha7 Nicotinic Acetylcholine Receptor; D009538:Nicotine; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human