Abstract
The mammalian skin is the largest organ of the body and its outermost layer, the epidermis, undergoes dynamic lifetime renewal through the activity of somatic stem cell populations. The EGFR-Ras-Raf pathway has a well-described role in skin development and tumor formation. While research mainly focuses on its role in cutaneous tumor initiation and maintenance, much less is known about Ras signaling in the epidermal stem cells, which are the main targets of skin carcinogenesis. In this review, we briefly discuss the properties of the epidermal stem cells and review the role of EGFR-Ras-Raf signaling in keratinocyte stem cells during homeostatic and pathological conditions.
Highlights
The stratified, multilayered epidermis is the outermost barrier of the skin that protects the body from the environment
This review provides an overview of the characteristics of hair follicle stem cells (HFSC) and interfollicular epidermis (IFE)
Continuously activated signaling in most of the cases leads to hair loss, supporting the theory that a cyclical on/off switch of this pathway is required for proper hair cycle progression [75,98,99,105,106,107] (Table 1)
Summary
The stratified, multilayered epidermis is the outermost barrier of the skin that protects the body from the environment. Terminally differentiated cells at the surface of the interfollicular epidermis (IFE) are continuously replaced by proliferative cells of the basal layer [1]. The constant renewal of the IFE and the rhythmic regeneration of the hair follicle governed by stem cells make the epidermis a powerful model for studying the behavior and signaling of adult stem cells in homeostatic and pathologic conditions [3]. This review provides an overview of the characteristics of hair follicle stem cells (HFSC) and IFE progenitor cells and of the role of the EGFR-Ras-Raf signaling pathway during normal skin maintenance, epidermis regeneration and carcinogenesis
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