NNK enhances cell migration through α7-nicotinic acetylcholine receptor accompanied by increased of fibronectin expression in gastric cancer.

Abstract

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.

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.

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.

CONCLUSIONS:

NNK enhanced gastric cancer metastasis through alpha7-nAChR and fibronectin-one of the hallmarks of epithelial mesenchymal transition.

• Authors: Weu Wang, Hung Chin-Sheng, Li-Jen Kuo, Po-Li Wei, Yung-Chang Lien, Feng-Yen Lin, Hui-Hsiung Liu, Yuan-Soon Ho, Chih-Hsiung Wu, Yu-Jia Chang
• Journal: Annals of surgical oncology (Ann Surg Oncol) Vol. 19 Suppl 3 Pg. S580-8 (Jul 2012) ISSN: 1534-4681 [Electronic] United States
• PMID: 21969082 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Carcinogens
• Chrna7 protein, human
• Fibronectins
• Nitrosamines
• Receptors, Nicotinic
• alpha7 Nicotinic Acetylcholine Receptor
• nAChR alpha9
• methyllycaconitine
• 4-(N-methyl-N-nitrosamino)-1-(3-pyridyl)-1-butanone
• Aconitine

Topics

• Aconitine (analogs & derivatives, pharmacology)
• Adenocarcinoma (metabolism)
• Carcinogens (pharmacology)
• Cell Line, Tumor
• Cell Movement (drug effects)
• Fibronectins (drug effects, genetics, metabolism)
• Genetic Vectors
• Humans
• Nitrosamines (pharmacology)
• Plasmids
• RNA Interference
• Receptors, Nicotinic (genetics, metabolism)
• Stomach Neoplasms (metabolism)
• Transfection
• Up-Regulation (drug effects)
• alpha7 Nicotinic Acetylcholine Receptor