TY - JOUR TI - CERKL is Upregulated in Cutaneous Squamous Cell Carcinoma and Maintains Cellular Sphingolipids and Resistance to Oxidative Stress AU - Meyer, J. M. AU - Lee, E. AU - Celli, A. AU - Park, K. AU - Cho, R. AU - Lambert, W. AU - Pitchford, M. AU - Gordon, M. AU - Tsai, K. AU - Cleaver, J. AU - Arron, S. T. AU - Mauro, T. M. T2 - British Journal of Dermatology AB - Background Ceramide Kinase-Like Protein (CERKL) was originally described in retinal tissue. CERKL has been shown to protect cells from oxidative stress, and mutations in CERKL underlie the inherited disease, retinitis pigmentosa. CERKL expression maintains cellular sphingolipids via an unknown mechanism. Objectives: To determine whether CERKL is expressed in epidermis and cutaneous squamous cell carcinoma (cSCC) and whether CERKL expression affects cSCC sphingolipid metabolism and susceptibility to oxidative stress. Methods CERKL expression was determined by RNA-Seq, qPCR and immunohistochemistry. CERKL was knocked down in cSCC cells using siRNA. Sphingolipid content was analyzed by liquid chromatography-mass spectrometry (LC-MS). Oxidative stress was induced by treatment with H2O2, and apoptosis was measured using flow cytometry to determine annexin v binding. Results CERKL mRNA and protein are highly expressed in actinic keratosis and cSCC in comparison with normal epidermis. CERKL also is expressed in metabolically active epithelial cells in normal hair bulbs and sebaceous glands. CERKL knockdown in cultured cSCC cells reduces cellular sphingolipid content and enhances susceptibility to oxidative stress. Conclusions These findings suggest that CERKL may be important in cSCC progression and could lead to novel strategies for prevention and treatment of cSCC. DO - https://doi.org/10.1111/bjd.19707 DP - Wiley Online Library VL - n/a IS - n/a LA - en SN - 1365-2133 UR - https://onlinelibrary.wiley.com/doi/abs/10.1111/bjd.19707 Y2 - 2020/12/04/22:13:06 ER -