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  • Title: Nicotine enhances colon cancer cell migration by induction of fibronectin.
    Author: Wei PL, Kuo LJ, Huang MT, Ting WC, Ho YS, Wang W, An J, Chang YJ.
    Journal: Ann Surg Oncol; 2011 Jun; 18(6):1782-90. PubMed ID: 21210228.
    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.
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