Abstract
Tobacco smoking is the major risk factor for oral squamous cell carcinoma (OSCC). Previously, we found that nicotine up-regulates peroxiredoxin 1 (Prx1), an important antioxidant enzyme, and nuclear factor kappa B (NFκB) in OSCC cells. However, the molecular mechanism of Prx1 in oral carcinogenesis remains obscure. To improve our understanding of the functional role of Prx1 during the cascade of tobacco-associated oral carcinogenesis, we characterized Prx1, NFκB, and epithelial-to-mesenchymal transition (EMT) markers including E-cadherin, vimentin and Snail in 30 primary oral tumors (15 from smokers with OSCC and 15 from non-smokers with OSCC) and 10 normal oral mucosa specimens from healthy individuals. The expression levels of Prx1, nuclear NFκB, vimentin and Snail were higher in the tumors from smokers with OSCC than in those from non-smokers with OSCC or the healthy controls. The expression levels of E-cadherin showed an opposite trend. Prx1 silencing suppressed the nicotine-induced EMT, cell invasion and migration in SCC15 cells in vitro. Furthermore, Prx1 activated the NFκB pathway in SCC15 cells. Prx1 might therefore play an oncogenic role in tobacco-related OSCC and thus serve as a target for chemopreventive and therapeutic interventions.
Highlights
Oral squamous cell carcinoma (OSCC) is the sixth most common cancer and represents a huge health burden worldwide [1]
The epithelialto-mesenchymal transition (EMT) markers E-cadherin, vimentin and Snail are altered in human oral squamous cell carcinoma (OSCC) tissues
The smokers and non-smokers with OSCC had lower expression levels of E-cadherin mRNA and higher expression levels of vimentin and Snail mRNAs compared with the healthy individuals (Figure 1A)
Summary
Oral squamous cell carcinoma (OSCC) is the sixth most common cancer and represents a huge health burden worldwide [1]. The overall survival rate of patients with OSCC is low because of late diagnoses, low therapeutic response rates, and high recurrence [2]. Tobacco smoking is the major risk factor for OSCC and is associated with tumor development, invasion, and metastasis, which are responsible for the high recurrence and poor prognosis [3, 4]. EMT involves a series of morphological alterations (losses of cell-cell junctions and cell polarity) and molecular changes including the down-regulation of epithelial cell markers (e.g., E-cadherin) and the upregulation of mesenchymal adhesion and cytoskeletal proteins (e.g., vimentin) and transcription factors (e.g., Snail) [5, 6]. Enhanced EMT is associated with poor overall and metastasis-free survival in OSCC [7]. The long-term use of nicotine can enhance the expression of Snail, an important EMT regulator, in OSCC cells [8, 9]
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