Abstract
BackgroundThe mechanisms of neuronal protein γ-synuclein (SNCG) in the malignancy of oral squamous cell carcinoma (OSCC) are not clear. This study tested the hypothesis that SNCG is involved in nicotine-induced malignant behaviors of OSCC. The effect of nicotine on SNCG expression and epithelial-to-mesenchymal transition (EMT) markers were examined.MethodsShort hairpin RNA (shRNA) and an antagonist specific for α7-nicotine acetylcholine receptors (α7-nAChRs) were used to examine the role of α7-nAChRs in mediating the effects of nicotine. Knockdown of SNCG in nicotine-treated cells was performed to investigate the role of SNCG in cancer malignancy. The in vivo effect of nicotine was examined using a nude mouse xenotransplantation model.ResultsNicotine increased SNCG expression in a time- and dose-dependent manner. Nicotine treatment also increased E-cadherin and ZO-1 and decreased fibronectin and vimentin expression. After specific knockdown of α7-nAChRs and inhibition of the PI3/AKT signal, the effect of nicotine on SNCG expression was attenuated. Silencing of SNCG abolished nicotine-induced invasion and migration of OSCC cells. The xenotransplantation model revealed that nicotine augmented tumor growth and SNCG expression.ConclusionNicotine upregulated SNCG expression by activating the α7-nAChRs/PI3/AKT signaling that are participated in nicotine-induced oral cancer malignancy.
Highlights
The mechanisms of neuronal protein γ-synuclein (SNCG) in the malignancy of oral squamous cell carcinoma (OSCC) are not clear
Nicotine up‐regulates SNCG expression in OSCC cells To determine whether SNCG is a nicotine-responsive protein, YD8 and OEC-M1 OSCC cells were treated with different doses of nicotine for 72 h followed by Western blot analysis of SNCG levels
OSCC cells were treated with nicotine for different time periods and it was observed that nicotine time-dependently upregulated SNCG expression (Fig. 1a)
Summary
The mechanisms of neuronal protein γ-synuclein (SNCG) in the malignancy of oral squamous cell carcinoma (OSCC) are not clear. This study tested the hypothesis that SNCG is involved in nicotine-induced malignant behaviors of OSCC. Each year more than 500,000 patients are Cigarette smoking is a risk factor for oral squamous cell carcinogenesis and progression [4,5,6], and nicotine is the major component of tobacco in cigarettes [7, 8]. In the CNS, binding of nicotine to specific nAChRs leads to distinct electrophysiological and pharmacological properties. In cancer cells, binding of nicotine to nAChRs stimulates intracellular signaling pathways in a tissue-specific manner, activates downstream mitogenic pathways, and upregulates the expression of growth factors [11]
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