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01-07-2012 | Translational Research and Biomarkers

NNK Enhances Cell Migration through α7-nicotinic Acetylcholine Receptor Accompanied by Increased of Fibronectin Expression in Gastric Cancer

Authors: Weu Wang, MD, Hung Chin-Sheng, MD, Li-Jen Kuo, MD, Po-Li Wei, MD, Yung-Chang Lien, MD, Feng-Yen Lin, PhD, Hui-Hsiung Liu, MD, PhD, Yuan-Soon Ho, PhD, Chih-Hsiung Wu, MD, Yu-Jia Chang, PhD

Published in: Annals of Surgical Oncology | Special Issue 3/2012

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.

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Title: NNK Enhances Cell Migration through α7-nicotinic Acetylcholine Receptor Accompanied by Increased of Fibronectin Expression in Gastric Cancer
Authors: Weu Wang, MD
Hung Chin-Sheng, MD
Li-Jen Kuo, MD
Po-Li Wei, MD
Yung-Chang Lien, MD
Feng-Yen Lin, PhD
Hui-Hsiung Liu, MD, PhD
Yuan-Soon Ho, PhD
Chih-Hsiung Wu, MD
Yu-Jia Chang, PhD
Publication date: 01-07-2012
Publisher: Springer-Verlag
Published in: Annals of Surgical Oncology / Issue Special Issue 3/2012
Print ISSN: 1068-9265
Electronic ISSN: 1534-4681
DOI: https://doi.org/10.1245/s10434-011-2064-x

At a glance: The STEP trials

Springer Medicine

NNK Enhances Cell Migration through α7-nicotinic Acetylcholine Receptor Accompanied by Increased of Fibronectin Expression in Gastric Cancer

Abstract

Background

Methods

Results

Conclusions

At a glance: The STEP trials

Springer Medicine

Abstract

Background

Methods

Results

Conclusions

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