Role of sphingolipids in non-melanoma skin cancer

Non-melanoma skin cancer (NMSC) is the most common cancer in the world and its incidence continues to rise. NMSC includes two main types, basal cell carcinoma (BCC) and squamous cell carcinoma (SCC), both of which arise from malignant keratinocytes, the major cell type in the epidermis of the skin. Most cases of NMSC can be cured by existing new surgical techniques and chemo- or radiotherapy. However, NMSC remains a leading cause of cancer-related deaths in the United States and worldwide likely due to its extremely high incidence and recurrence rate, and limited availability of effective therapies for advanced cases. Therefore, we still need a better understanding of its pathogenesis and the development of novel and effective approaches to diagnosis, prevention, and treatment. Like many other cancers, NMSC results from dysregulation of the proliferation, differentiation, and apoptosis of cells that it originates from. Emerging evidence suggests that sphingolipids play an important role in regulating these cellular responses of keratinocytes and the homeostasis of the epidermis. In this review, we will discuss the role for sphingolipids and their metabolizing enzymes in regulating the proliferation, differentiation, and apoptosis of epidermal keratinocytes and the potential role of sphingolipids in NMSC prevention and/or therapy.