Nicotine Promotes Cell Migration Through Alpha7 Nicotinic Acetylcholine Receptor in Gastric Cancer Cells

Lien, Yung Chang; Wang, Weu; Kuo, Li Jen; Liu, Jun Jen; Wei, Po Li; Ho, Yuan Soon; Ting, Wen Chien; Wu, Chih Hsiung; Chang, Yu Jia

doi:10.1245/s10434-011-1598-2

Cited by 51 publications

(38 citation statements)

References 35 publications

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“…The findings that nicotine did not induce migration in quiescent A549 cancer cells in the absence of HGF is inconsistent with the results of previous studies, which observed that nicotine itself exerts a pro-migratory effect in various types of cancer cells (10,(12)(13)(14)16,17). The reasoning behind the inconsistent results between the present study and previous studies remains uncertain, however, it may be attributed to differences in the experimental protocol.…”

Section: Discussioncontrasting

confidence: 99%

“…Recent evidence suggests that the tumor-promoting effects of nicotine result in increased proliferation, invasion, mesenchymal transition (EMT) and angiogenesis, and decreased cell death and apoptosis (4,(9)(10)(11)(12)(13)(14)(15)(16)(17). However, the molecular mechanisms by which nicotine promotes tumor progression are not yet fully understood.…”

Section: Introductionmentioning

confidence: 99%

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Nicotine enhances hepatocyte growth factor-mediated lung cancer cell migration by activating the α7 nicotine acetylcholine receptor and phosphoinositide kinase-3-dependent pathway

et al. 2015

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Abstract. Cigarette smoking not only promotes lung carcinogenesis, but it has also been demonstrated to promote the progression of lung cancer. Despite nicotine being a major component of cigarette smoke, it is not carcinogenic when acting alone. Instead, it is believed to function as a tumor promoter. Due to the fatal consequences of lung cancer being primarily associated with the processes of invasion and metastasis, the present study aimed to determine the effect of nicotine on the migratory activity of lung cancer cells. The effect of nicotine on the migration of lung cancer A549 cells was evaluated by a wound healing assay. Hepatocyte growth factor (HGF) was used as a pro-migratory stimulus. During several of the experiments, specific inhibitors of α7-nicotine acetylcholine receptor (α7-nAchR), phosphoinositide kinase-3 (PI3K) and extracellular signal-related kinase (ERK)1/2 were included. The phosphorylation levels of Akt and ERK1/2 were examined using a cell-based protein phosphorylation assay. It was observed that nicotine did not induce cell migration by itself, but that it instead promoted HGF-induced cell migration. The effects of nicotine were inhibited by the pretreatment of the cells with the α7-nAchR inhibitor, methyllycaconitine, and the PI3K inhibitor, LY294002. The mitogen-activated protein kinase/ERK kinase kinase inhibitor exerted modest, but non-significant inhibitory activity on the effect of nicotine. Nicotine did not induce Akt phosphorylation by itself, but instead promoted the HGF-induced phosphorylation of Akt. It was also observed that nicotine had no effect on ERK1/2 phosphorylation. The results from the present study indicate that nicotine, when alone, does not have a pro-migratory function, but instead enhances responsiveness to the pro-migratory stimulus emitted by HGF. The current study provides an insight into the mechanism of tumor promotion by demonstrating that nicotine and α7-nAchRs act in synergy with the HGF-induced PI3K/Akt signaling pathway, increasing the sensitivity of lung cancer cells to HGF, and thereby promoting cell migration, a vital step in invasion and metastasis. IntroductionLung cancer has one of the lowest survival rates of all types of cancer, accounting for 1.59 million mortalities in the world in 2012 (1). Smoking, particularly of cigarettes, is estimated to cause 87% of the lung cancer mortalities in men, and 70% of the lung cancer mortalities in women (2). Cigarette smoke contains numerous carcinogens, of which, polycyclic aromatic hydrocarbons and the tobacco-specific nitrosamine, 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol, are likely to serve major roles (3). However, recent evidence suggests that cigarette smoking not only promotes lung carcinogenesis, but that it also promotes the progression of lung cancer (4). For example, continued smoking during lung cancer treatment has been associated with decreased survival (5), while smoking cessation during the treatment improves the therapeutic outcome (6). Furthermore, cigarette smoking increases the r...

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Section: Discussioncontrasting

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Nicotine enhances hepatocyte growth factor-mediated lung cancer cell migration by activating the α7 nicotine acetylcholine receptor and phosphoinositide kinase-3-dependent pathway

et al. 2015

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“…Nicotine caused up-regulation of VCAM-1, MMP-2, and MMP-9 through the ␣7-nAChR-JNK pathway (58), and stimulation of cell migration through ␣7 nicotinic acetylcholine receptor in gastric cancer cells (59). Similarly, in our recent finding (Fig.…”

Section: Discussionsupporting

confidence: 76%

Association of MMP7 −181A→G Promoter Polymorphism with Gastric Cancer Risk

Kesh

Subramanian

Ghosh

et al. 2015

Journal of Biological Chemistry

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Background: Effect of tobacco carcinogen nicotine on MMP7 transcription and gastric cancer risk remains unknown. Results: Preferential binding of pCREB, induced by nicotine, to G-allele promoter enhanced the transcription and thus aggravated gastric cancer risk. Conclusion: Nicotine shows an additive effect over MMP7 GG genotype toward gastric cancer risk. Significance: These findings may help in the clinical management of gastric cancer.

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“…Although we observed that nicotine induced A549 cell migration and invasion by up-regulating a5-nAChR, the downstream mechanism of a5-nAChR-medicated cell migration and invasion induced by nicotine treatment is unclear. Nicotine could induce a5-nAChR over-expression and epithelial-mesenchymal transition (EMT) repression (Lien et al, 2011;Wu et al, 2013;Zou et al, 2013), but it is unknown whether EMT plays a critical role in the downstream of nicotine-induced NSCLC cell migration and invasion through a5-nAChR. Further study should be performed to answer this question.…”

Section: Discussionmentioning

confidence: 99%

α5-nAChR modulates nicotine-induced cell migration and invasion in A549 lung cancer cells

Sun

2015

Experimental and Toxicologic Pathology

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Nicotine Promotes Cell Migration Through Alpha7 Nicotinic Acetylcholine Receptor in Gastric Cancer Cells

Abstract: Tobacco-specific mitogen, nicotine, enhanced gastric cancer metastasis through alpha7-nAChR and suppression of E-cadherin level-one of the hallmarks of epithelial to mesenchymal transition. Therefore, patients with gastric cancer should avoid smoking.

Cited by 51 publications

References 35 publications

Nicotine enhances hepatocyte growth factor-mediated lung cancer cell migration by activating the α7 nicotine acetylcholine receptor and phosphoinositide kinase-3-dependent pathway

Nicotine enhances hepatocyte growth factor-mediated lung cancer cell migration by activating the α7 nicotine acetylcholine receptor and phosphoinositide kinase-3-dependent pathway

Association of MMP7 −181A→G Promoter Polymorphism with Gastric Cancer Risk

α5-nAChR modulates nicotine-induced cell migration and invasion in A549 lung cancer cells

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