Abstract
Cutaneous squamous cell carcinoma (SCC) is a common cancer that significantly decreases the quality of life. It is known that external stimulus such as ultraviolet (UV) radiation induces cutaneous SCC via provoking oxidative stress. NAD(P)H dehydrogenase 1 (NQO1) is a ubiquitous flavoenzyme that functions as a guardian against oxidative stress. However, the effect of NQO1 on cutaneous SCC is not clearly elucidated. In this study, we investigated the effect of NQO1 on cutaneous SCC cells using the recombinant adenoviruses that can upregulate and/or downregulate NQO1 expression. Overexpression of NQO1 resulted in significant decrease of cell proliferation and colony forming activity of SCC lines (SCC12 and SCC13 cells). By contrast, knockdown of NQO1 increased the cell proliferation and colony forming activity. Accordingly, the levels of proliferation-related regulators, such as Cyclin D1, Cyclin E, PCNA, SOX2, and p63, were decreased by the overexpression of NQO1, while those were increased by knockdown of NQO1. In addition, NQO1 affected the invasion and migration of SCC cells in a very similar way, with the regulation of epithelial-mesenchymal transition- (EMT-) related molecules, including E-cadherin, N-cadherin, Vimentin, Snail, and Slug. Finally, the overexpression of NQO1 decreased the level of phosphorylated AKT, JNK, and p38 MAPK, while the knockdown of NQO1 increased the level of phosphorylated signaling molecules. Based on these data, NQO1 has tumor suppressive function in cutaneous SCC cells.
Highlights
Cutaneous squamous cell carcinoma (SCC) is a common cancer, which is originated from the differentiated keratinocytes in upper layers of epidermis
We examined the expression level of NQO1 by immunohistochemistry in the normal and SCC lesional area obtained from the same patient
We demonstrated the tumor suppressive function of NQO1 in cutaneous SCC cells
Summary
Cutaneous squamous cell carcinoma (SCC) is a common cancer, which is originated from the differentiated keratinocytes in upper layers of epidermis. It is the second most frequent type among the nonmelanoma skin cancers, influencing the quality of life considerably [1, 2]. NQO1 functions as a guardian against oxidative stress in various ways, such as detoxifying the highly reactive quinones, maintaining lipid-soluble antioxidants in reduced forms, and stabilizing the tumor suppressor p53 [12]. It has been reported that the deletion of NQO1 gene makes mice more susceptible to oxidative stress and frequently develop skin tumor upon carcinogen exposure [13]. It has been reported that the knockdown of BioMed Research International
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