Journal article
Epidermal FABP Prevents Chemical-Induced Skin Tumorigenesis by Regulation of TPA-Induced IFN/p53/SOX2 Pathway in Keratinocytes
Journal of investigative dermatology, Vol.138(9), pp.1925-1934
09/01/2018
DOI: 10.1016/j.jid.2018.02.041
PMCID: PMC6109432
PMID: 29559340
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-acetateeinduced 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-beta and IFN-lambda 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.
Details
- Title: Subtitle
- Epidermal FABP Prevents Chemical-Induced Skin Tumorigenesis by Regulation of TPA-Induced IFN/p53/SOX2 Pathway in Keratinocytes
- Creators
- Yuwen Zhang - University of LouisvilleJiaqing Hao - University of LouisvilleJun Zeng - University of LouisvilleQiang Li - Shandong Provincial HospitalEnyu Rao - University of LouisvilleYanwen Sun - University of LouisvilleLianliang Liu - University of LouisvilleAnita Mandal - University of LouisvilleV. Douglas Landers - University of LouisvilleRebecca J. Morris - University of MinnesotaMargot P. Cleary - University of MinnesotaJill Suttles - University of LouisvilleBing Li - University of Louisville
- Resource Type
- Journal article
- Publication Details
- Journal of investigative dermatology, Vol.138(9), pp.1925-1934
- Publisher
- Elsevier
- DOI
- 10.1016/j.jid.2018.02.041
- PMID
- 29559340
- PMCID
- PMC6109432
- ISSN
- 0022-202X
- eISSN
- 1523-1747
- Number of pages
- 10
- Grant note
- Hormel Foundation R01CA177679 / NATIONAL CANCER INSTITUTE; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Cancer Institute (NCI) R01CA177679; R01CA180986 / National Cancer Institute (Bethesda, MD); United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Cancer Institute (NCI)
- Language
- English
- Date published
- 09/01/2018
- Academic Unit
- Pathology; Surgery
- Record Identifier
- 9984695802702771
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