Gamma synuclein is a novel nicotine responsive protein in oral cancer malignancy.
- Resource Type
- Article
- Authors
- Hsu, Chia-Chen; Su, Yu-Fu; Tsai, Kuo-Yang; Kuo, Feng-Chih; Chiang, Chi-Fu; Chien, Chu-Yen; Chen, Ying-Chen; Lee, Chien-Hsing; Wu, Yu-Chiao; Wang, Kun; Liu, Shyun-Yeu; Shieh, Yi-Shing
- Source
- Cancer Cell International. 7/10/2020, Vol. 20 Issue 1, p1-12. 12p.
- Subject
- *NICOTINE
*ORAL cancer
*CANCER
*EPITHELIAL-mesenchymal transition
*CHOLINERGIC receptors
- Language
- ISSN
- 1475-2867
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. [ABSTRACT FROM AUTHOR]