title: Snail interacts with Id2 in the regulation of TNF-α-induced cancer cell invasion and migration in OSCC.
abstract: The inflammatory tumor microenvironment has been identified to play a pivotal role in tumor development and metastasis. Tumor necrosis factor-α (TNF-α) is one of the key cytokines that regulate the inflammatory processes in tumor promotion. In the current study, we treated three oral squamous cell carcinoma (OSCC) cell lines with TNF-α to study its role in inflammation-induced tumor progression. Here we show that TNF-α induces stabilization of the transcriptional repressor Snail and activates NF-κB pathway in the three OSCC cell lines. These activities resulted in the increased motility and invasiveness of three OSCC cell lines. In addition, upon dealing with TNF-α for the indicated time, three OSCC cell lines underwent epithelial-to-mesenchymal transition (EMT), in which they presented a fibroblast-like phenotype and had a decreased expression of epithelial marker (E-cadherin) and an increased expression of mesenchymal marker (vimentin). We further demonstrated that TNF-α can up-regulate the expression of Id2 while inducing an EMT in oral cancer cells. Finally, we showed that Id2 interacted with Snail which may constrain Snail-dependent suppression of E-cadherin. In conclusion, our study indicates that TNF-α induces Snail stabilization is dependent on the activation of NF-κB pathway and results in increasing cell invasion and migration in OSCC cells. Id2 may contribute to regulate the function of Snail during TNF-α-mediated EMT in OSCC. These findings have significant implications for inflammation-induced tumor promotion in OSCC.
authors.affiliation: Department of Oral Medicine, School of Stomatology, Wannan Medical College Wuhu, People's Republic of China.
authors.forename: Jing-Ping
authors.initials: JP
authors.lastname: Zhou
authors.affiliation: Department of Oncology IV, First Hospital of Shijiazhuang Shijiazhuang, People's Republic of China.
authors.forename: Zhen-Lin
authors.initials: ZL
authors.lastname: Gao
authors.affiliation: Jiangsu Key Laboratory of Oral Diseases, Nanjing Medical University Nanjing, People's Republic of China ; Department of Basic Science of Stomatology, Affiliated Hospital of Stomatology, Nanjing Medical University Nanjing, People's Republic of China.
authors.forename: Mei-Ling
authors.initials: ML
authors.lastname: Zhou
authors.affiliation: Jiangsu Key Laboratory of Oral Diseases, Nanjing Medical University Nanjing, People's Republic of China ; Department of Basic Science of Stomatology, Affiliated Hospital of Stomatology, Nanjing Medical University Nanjing, People's Republic of China.
authors.forename: Meng-Ying
authors.initials: MY
authors.lastname: He
authors.affiliation: Jiangsu Key Laboratory of Oral Diseases, Nanjing Medical University Nanjing, People's Republic of China ; Department of The First Outpatient, Affiliated Hospital of Stomatology, Nanjing Medical University Nanjing, People's Republic of China.
authors.forename: Xiao-Hui
authors.initials: XH
authors.lastname: Xu
authors.affiliation: Department of Oral and Maxillofacial Surgery, The First Affiliated Hospital of Wannan Medical College Wuhu, People's Republic of China.
authors.forename: De-Tao
authors.initials: DT
authors.lastname: Tao
authors.affiliation: Jiangsu Key Laboratory of Oral Diseases, Nanjing Medical University Nanjing, People's Republic of China ; Department of Basic Science of Stomatology, Affiliated Hospital of Stomatology, Nanjing Medical University Nanjing, People's Republic of China.
authors.forename: Cong-Chong
authors.initials: CC
authors.lastname: Yang
authors.affiliation: Jiangsu Key Laboratory of Oral Diseases, Nanjing Medical University Nanjing, People's Republic of China ; Department of Basic Science of Stomatology, Affiliated Hospital of Stomatology, Nanjing Medical University Nanjing, People's Republic of China.
authors.forename: Lai-Kui
authors.initials: LK
authors.lastname: Liu
keywords: Epithelial-to-mesenchymal transition; Id2; Snail; oral squamous cell carcinoma; tumor necrosis factor-α