EGFR Activation and Ultraviolet Light‐Induced Skin Carcinogenesis

[摘要] The epidermal growth factor receptor (EGFR) regulates the proliferation of keratinocytes through multiple mechanisms that differ depending on the localization of the cell within the skin. Ultraviolet (UV) irradiation, themain etiologic factor in the development of skin cancer, also activatesthe receptor. In this review, we discuss how the UV-induced activationof EGFR regulates the response of the skin to UV.UV-induced EGFRactivation increases keratinocyte proliferation, suppresses apoptosis, andaugments and accelerates epidermal hyperplasia in response to UV.Pharmacological inhibition of the UV-induced activation of EGFR ina genetically initiated mouse skin tumorigenesis model suppressestumorigenesis and the activation of mitogen-activated protein (MAP) kinasesand phosphatidyl inositol-3-kinase (PI3K)/AKT signaling pathways. EGFRhas pleiotropic, complex, and cell-type-specific functions in cutaneouskeratinocytes; suggesting that the receptor is an appropriate target forthe development of molecularly targeted therapies for skin cancer and other pathologies.

[学科分类] 基础医学