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Nicotine promotes cervical metastasis of oral cancer by regulating peroxiredoxin 1 and epithelial–mesenchymal transition in mice

Authors Wang M, Niu W, Qi M, Chen H, Zhang M, Wang C, Ge L, Yang J, Miao C, Shi N, Chen T, Tang X

Received 10 November 2018

Accepted for publication 13 February 2019

Published 1 May 2019 Volume 2019:12 Pages 3327—3338

DOI https://doi.org/10.2147/OTT.S194129

Checked for plagiarism Yes

Review by Single-blind

Peer reviewers approved by Dr Andrew Yee

Peer reviewer comments 2

Editor who approved publication: Dr Federico Perche


Min Wang,1 Wenwen Niu,2 Moci Qi,1 Hui Chen,1 Min Zhang,1 Chunxiao Wang,1 Lihua Ge,1 Jing Yang,1 Congcong Miao,1 Ni Shi,3 Tong Chen,3 Xiaofei Tang1

1Beijing Institute of Dental Research, Beijing Stomatological Hospital and School of Stomatology, Capital Medical University, Beijing 100050, People’s Republic of China; 2Beijing Shibalidian Community Hospital, Beijing, People’s Republic of China; 3Division of Medical Oncology, Department of Internal Medicine, The Arthur G. James Cancer Hospital and Richard J. Solove Research Institute, The Ohio State University, Columbus, OH 43210, USA

Background: Tobacco is a major risk factor for oral squamous cell carcinoma (OSCC). However, the role of nicotine in OSCC is not completely understood.
Materials and methods: To analyze the mechanisms of nicotine-induced cervical metastasis, we investigated whether nicotine induced invasion, migration, and epithelial–mesenchymal transition (EMT) via regulating peroxiredoxin 1 (Prx1) in CAL 27 cells. In addition, we established a mouse model to confirm the roles of nicotine in regulating Ets1/Prx1/EMT signaling in OSCC metastasis.
Results: We showed that nicotine induced CAL 27 cell invasion, migration, EMT, and Prx1 and Ets1 expression. Prx1 knockdown inhibited cell invasion, migration, and EMT. Ets1 silencing downregulated Prx1 expression and EMT. Prx1 and Ets1 were shown to interact in CAL 27 cells treated with nicotine, and nicotine could significantly upregulate the binding of the transcription factor Ets1 to the Prx1 gene promoter region. Additionally, an in vivo study showed that nicotine induced tumor metastasis and EMT. Prx1 knockdown inhibited cervical metastasis rates and EMT progression. No significant differences in metastasis rates and EMT-related marker expression levels were observed between vehicle- and nicotine-treated mice.
Conclusion: The results indicate that nicotine promotes cervical lymph node metastasis through regulating Ets1/Prx1/EMT signaling during OSCC pathogenesis; consequently, Prx1 may represent a potential target for the prevention and treatment of OSCC.

Keywords: oral squamous cell carcinoma, peroxiredoxin 1, metastasis, epithelial–mesenchymal transition, mouse model


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