1. Epidermal FABP Prevents Chemical-Induced Skin Tumorigenesis by Regulation of TPA-Induced IFN/p53/SOX2 Pathway in Keratinocytes.
- Author
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Zhang Y, Hao J, Zeng J, Li Q, Rao E, Sun Y, Liu L, Mandal A, Landers VD, Morris RJ, Cleary MP, Suttles J, and Li B
- Subjects
- Animals, Carcinogenesis, Epidermis metabolism, Epidermis pathology, Fatty Acid-Binding Proteins biosynthesis, Interferon-beta metabolism, Keratinocytes pathology, Male, Mice, Mice, Inbred C57BL, Neoplasm Proteins biosynthesis, Neoplasms, Experimental, RNA, Neoplasm genetics, SOXB1 Transcription Factors metabolism, Skin Neoplasms metabolism, Tetradecanoylphorbol Acetate toxicity, Tumor Suppressor Protein p53 metabolism, Fatty Acid-Binding Proteins genetics, Gene Expression Regulation, Neoplastic, Interferon-beta genetics, Keratinocytes metabolism, Neoplasm Proteins genetics, SOXB1 Transcription Factors genetics, Skin Neoplasms genetics, Tumor Suppressor Protein p53 genetics
- 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., (Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.)
- Published
- 2018
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