J M Meyer1, E Lee1, A Celli1, K Park1, R Cho2, W Lambert3, M Pitchford1, M Gordon1, K Tsai4, J Cleaver5, S T Arron1, T M Mauro1. 1. Dermatology Service, VA Medical Center, Department of Dermatology, UC San Francisco, CA, USA. 2. Department of Dermatology, UC San Francisco, CA, USA. 3. Pathology and Laboratory Medicine, Rutgers University, Newark, NJ, USA. 4. Moffitt Cancer Center, Tampa, FL, USA. 5. Departments of Dermatology and Pharmaceutical Chemistry, UC San Francisco, CA, USA.
Abstract
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 H2 O2 , 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. This article is protected by copyright. All rights reserved.
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 H2 O2 , 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. This article is protected by copyright. All rights reserved.
Authors: Sébastien de Feraudy; Imenne Boubakour-Azzouz; Sylvie Fraitag; Mark Berneburg; Loretta Chan; Kevin Chew; Carol L Clericuzio; Bari Cunningham; Whitney D Tope; James E Cleaver Journal: Am J Dermatopathol Date: 2010-04 Impact factor: 1.533
Authors: Anna Celli; Donald S Mackenzie; Yongjiao Zhai; Chia-Ling Tu; Daniel D Bikle; Walter M Holleran; Yoshikazu Uchida; Theodora M Mauro Journal: J Invest Dermatol Date: 2012-01-26 Impact factor: 8.551
Authors: Vida Chitsazzadeh; Cristian Coarfa; Jennifer A Drummond; Tri Nguyen; Aaron Joseph; Suneel Chilukuri; Elizabeth Charpiot; Charles H Adelmann; Grace Ching; Tran N Nguyen; Courtney Nicholas; Valencia D Thomas; Michael Migden; Deborah MacFarlane; Erika Thompson; Jianjun Shen; Yoko Takata; Kayla McNiece; Maxim A Polansky; Hussein A Abbas; Kimal Rajapakshe; Adam Gower; Avrum Spira; Kyle R Covington; Weimin Xiao; Preethi Gunaratne; Curtis Pickering; Mitchell Frederick; Jeffrey N Myers; Li Shen; Hui Yao; Xiaoping Su; Ronald P Rapini; David A Wheeler; Ernest T Hawk; Elsa R Flores; Kenneth Y Tsai Journal: Nat Commun Date: 2016-08-30 Impact factor: 14.919