Molecular signaling cascades involved in nonmelanoma skin carcinogenesis.
Nonmelanoma skin cancer (NMSC) is the most common cancer worldwide and the incidence continues to rise, in part due to increasing numbers in high-risk groups such as organ transplant recipients and those taking photosensitizing medications. The most significant risk factor for NMSC is ultraviolet radiation (UVR) from sunlight, specifically UVB, which is the leading cause of DNA damage, photoaging, and malignant transformation in the skin. Activation of apoptosis following UVR exposure allows the elimination of irreversibly damaged cells that may harbor oncogenic mutations. However, UVR also activates signaling cascades that promote the survival of these potentially cancerous cells, resulting in tumor initiation. Thus, the UVR-induced stress response in the skin is multifaceted and requires coordinated activation of numerous pathways controlling DNA damage repair, inflammation, and kinase-mediated signal transduction that lead to either cell survival or cell death. This review focuses on the central signaling mechanisms that respond to UVR and the subsequent cellular changes. Given the prevalence of NMSC and the resulting health care burden, many of these pathways provide promising targets for continued study aimed at both chemoprevention and chemotherapy.
Department of Cellular and Molecular Physiology, The Pennsylvania State University College of Medicine, 500 University Drive, H166, Hershey, PA 17033, USA.
Robert P
RP
Feehan
Department of Cellular and Molecular Physiology, The Pennsylvania State University College of Medicine, 500 University Drive, H166, Hershey, PA 17033, USA.
Lisa M
LM
Shantz
D017209:Apoptosis; D004249:DNA Damage; D004789:Enzyme Activation; D006801:Humans; D007249:Inflammation / Q000150:complications; D016328:NF-kappa B / Q000378:metabolism; D009381:Neoplasms, Radiation-Induced / Q000378:metabolism / Q000473:pathology; D018384:Oxidative Stress; D050796:STAT3 Transcription Factor / Q000378:metabolism; D015398:Signal Transduction; D012878:Skin Neoplasms / Q000209:etiology / Q000378:metabolism* / Q000473:pathology; D014466:Ultraviolet Rays; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
D016328:NF-kappa B; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human; D048051:p38 Mitogen-Activated Protein Kinases
DNA damage response; apoptosis; nonmelanoma skin cancer; signal transduction; ultraviolet radiation.
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