EPAC mediates the dual role of cAMP signaling in melanoma

Cutaneous malignant melanoma arises from melanocytes, the pigment producing cells in the skin. Incidence of melanoma is increasing steadily during the past several decades. Melanoma is highly resistant to chemotherapy and patients with metastatic melanoma have a poor prognosis. Exposure to ultraviolet radiation (UV) from sunlight is the most common environmental risk factor for melanoma, although melanoma can occur in areas of the body not directly exposed to sun. Driver mutations in the mitogen-activated protein kinase (MAPK) pathway account for majority of melanomas [1]. Additionally, polymorphisms in the G-protein Coupled Receptor (GPCR) melanocortin-1 receptor gene MC1R, which are associated with fair skin and red hair, are risk factors for melanoma. These polymorphisms lead to defective repair of UV-induced DNA damage and reduced melanin production due to defective cyclic AMP (cAMP) signaling [2, 3]