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Cancer Cell International
Published in: Cancer Cell International 1/2020

Open Access 01-12-2020 | Oral Cancer | Primary research

Gamma synuclein is a novel nicotine responsive protein in oral cancer malignancy

Authors: Chia-Chen Hsu, Yu-Fu Su, Kuo-Yang Tsai, Feng-Chih Kuo, Chi-Fu Chiang, Chu-Yen Chien, Ying-Chen Chen, Chien-Hsing Lee, Yu-Chiao Wu, Kun Wang, Shyun-Yeu Liu, Yi-Shing Shieh

Published in: Cancer Cell International | Issue 1/2020

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Abstract

Background

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. The effect of nicotine on SNCG expression and epithelial-to-mesenchymal transition (EMT) markers were examined.

Methods

Short 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.

Results

Nicotine 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.

Conclusion

Nicotine upregulated SNCG expression by activating the α7-nAChRs/PI3/AKT signaling that are participated in nicotine-induced oral cancer malignancy.
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Metadata
Title
Gamma synuclein is a novel nicotine responsive protein in oral cancer malignancy
Authors
Chia-Chen Hsu
Yu-Fu Su
Kuo-Yang Tsai
Feng-Chih Kuo
Chi-Fu Chiang
Chu-Yen Chien
Ying-Chen Chen
Chien-Hsing Lee
Yu-Chiao Wu
Kun Wang
Shyun-Yeu Liu
Yi-Shing Shieh
Publication date
01-12-2020
Publisher
BioMed Central
Published in
Cancer Cell International / Issue 1/2020
Electronic ISSN: 1475-2867
DOI
https://doi.org/10.1186/s12935-020-01401-w

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