NNK Enhances Cell Migration through alpha 7-nicotinic Acetylcholine Receptor Accompanied by Increased of Fibronectin Expression in Gastric Cancer

作者：Wang Weu^*; Chin Sheng Hung; Kuo Li Jen; Wei Po Li; Lien Yung Chang; Lin Feng Yen; Liu Hui Hsiung; Ho Yuan Soon; Wu Chih Hsiung; Chang Yu Jia

来源：Annals of Surgical Oncology, 2012, 19(S3): S580-S588.

DOI：10.1245/s10434-011-2064-x

Background. In this study, we intended to dissect the mechanism of 4-(Methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK)-enhanced migration of gastric cancer. Smoking has been defined as a risk factor for gastric cancer. Tobacco-specific carcinogen, NNK, was reported to enhance cancer progression in gastric cancer. Currently, metastasis is the major issue for clinical cancer therapy, but the influence of NNK on the migration of gastric cancer remains to be determined. %26lt;br%26gt;Methods. The expression of nicotinic receptor in gastric cancer cells was identified by real-time polymerase chain reaction and Western blotting. The influence of NNK on migration of gastric cancer cells was evaluated by the transwell migration assay system. Receptor-mediated migration was studied by both inhibitor and small interfering RNA. %26lt;br%26gt;Results. Alpha7 nicotinic acetylcholine receptor, alpha7-nicotinic acetylcholine receptor (nAChR), was identified higher than alpha9-nAChR in gastric cancer cell lines, AGS cells. NNK enhanced significantly gastric cancer cell migration in transwell assay. We used inhibitor and siRNA to demonstrate that alpha7-nAChR mediated NNK-enhanced gastric cancer cell migration and upregulation of fibronectin were involved in NNK-enhanced migration of gastric cancer cells. Finally, we found that silenced fibronectin expression level inhibited the migratory ability in AGS cells. %26lt;br%26gt;Conclusions. NNK enhanced gastric cancer metastasis through alpha7-nAChR and fibronectin-one of the hallmarks of epithelial mesenchymal transition.

• 出版日期2012-7
• 单位河北医科大学