Epidermal FABP Prevents Chemical-Induced Skin Tumorigenesis by Regulation of TPA-Induced IFN/p53/SOX2 Pathway in Keratinocytes

Yuwen Zhang, Jiaqing Hao, Jun Zeng, Qiang Li, Enyu Rao, Yanwen Sun, Lianliang Liu, Anita Mandal, V. Douglas Landers, Rebecca J Morris, Margot P. Cleary, Jill Suttles, Bing Li

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Abstract

Skin lipids (e.g., fatty acids) are essential for normal skin functions. Epidermal FABP (E-FABP) is the predominant FABP expressed in skin epidermis. However, the role of E-FABP in skin homeostasis and pathology remains largely unknown. Herein, we utilized the 7,12-dimethylbenz(a)anthracene and 12-O-tetradecanolyphorbol-13-acetate–induced skin tumorigenesis model to assess the role of E-FABP in chemical-induced skin tumorigenesis. Compared to their wild-type littermates, mice deficient in E-FABP, but not adipose FABP, developed more skin tumors with higher incidence. 12-O-tetradecanolyphorbol-13-acetate functioning as a tumor promoter induced E-FABP expression and initiated extensive flaring inflammation in skin. Interestingly, 12-O-tetradecanolyphorbol-13-acetate -induced production of IFN-β and IFN-λ in the skin tissue was dependent on E-FABP expression. Further protein and gene expression arrays demonstrated that E-FABP was critical in enhancing IFN-induced p53 responses and in suppressing SOX2 expression in keratinocytes. Thus, E-FABP expression in skin suppresses chemical-induced skin tumorigenesis through regulation of IFN/p53/SOX2 pathway. Collectively, our data suggest an unknown function of E-FABP in prevention of skin tumor development, and offer E-FABP as a therapeutic target for improving skin innate immunity in chemical-induced skin tumor prevention.

Original languageEnglish (US)
Pages (from-to)1925-1934
Number of pages10
JournalJournal of Investigative Dermatology
Volume138
Issue number9
DOIs
StatePublished - Sep 2018

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    Zhang, Y., Hao, J., Zeng, J., Li, Q., Rao, E., Sun, Y., Liu, L., Mandal, A., Landers, V. D., Morris, R. J., Cleary, M. P., Suttles, J., & Li, B. (2018). Epidermal FABP Prevents Chemical-Induced Skin Tumorigenesis by Regulation of TPA-Induced IFN/p53/SOX2 Pathway in Keratinocytes. Journal of Investigative Dermatology, 138(9), 1925-1934. https://doi.org/10.1016/j.jid.2018.02.041