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Recent advances in the epidermal growth factor receptor/ligand system biology on skin homeostasis and keratinocyte stem cell regulation

  • Daisuke Nanba
    Correspondence
    Corresponding author at: Senior Research Fellow Center, Ehime University, Shitsukawa, Toon, Ehime 791-0295, Japan. Tel.: +81 89 960 5254; fax: +81 89 960 5256.
    Affiliations
    Senior Research Fellow Center, Ehime University, Shitsukawa, Toon, Ehime 791-0295, Japan

    Department of Cell Growth and Tumor Regulation, Proteo-Science Center (PROS), Ehime University, Shitsukawa, Toon, Ehime 791-0295, Japan
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  • Fujio Toki
    Affiliations
    Senior Research Fellow Center, Ehime University, Shitsukawa, Toon, Ehime 791-0295, Japan

    Department of Cell Growth and Tumor Regulation, Proteo-Science Center (PROS), Ehime University, Shitsukawa, Toon, Ehime 791-0295, Japan
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  • Yann Barrandon
    Affiliations
    Laboratory of Stem Cell Dynamics, Ecole Polytechnique Fédérale de Lausanne (EPFL), CH-1015 Lausanne, Switzerland

    Department of Experimental Surgery, Centre Hospitalier Universitaire Vaudois (CHUV), CH-1011 Lausanne, Switzerland
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  • Shigeki Higashiyama
    Correspondence
    Corresponding author at: Department of Cell Growth and Tumor Regulation, Proteo-Science Center, Ehime University, Shitsukawa, Toon, Ehime 791-0295, Japan. Tel.: +81 89 960 5253; fax: +81 89 960 5256.
    Affiliations
    Department of Cell Growth and Tumor Regulation, Proteo-Science Center (PROS), Ehime University, Shitsukawa, Toon, Ehime 791-0295, Japan

    Department of Biochemistry and Molecular Genetics, Graduate School of Medicine, Ehime University, Shitsukawa, Toon, Ehime 791-0295, Japan
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      Abstract

      The epidermal growth factor (EGF) receptor/ligand system stimulates multiple pathways of signal transduction, and is activated by various extracellular stimuli and inter-receptor crosstalk signaling. Aberrant activation of EGF receptor (EGFR) signaling is found in many tumor cells, and humanized neutralizing antibodies and synthetic small compounds against EGFR are in clinical use today. However, these drugs are known to cause a variety of skin toxicities such as inflammatory rash, skin dryness, and hair abnormalities. These side effects demonstrate the multiple EGFR-dependent homeostatic functions in human skin. The epidermis and hair follicles are self-renewing tissues, and keratinocyte stem cells are crucial for maintaining these homeostasis. A variety of molecules associated with the EGF receptor/ligand system are involved in epidermal homeostasis and hair follicle development, and the modulation of EGFR signaling impacts the behavior of keratinocyte stem cells. Understanding the roles of the EGF receptor/ligand system in skin homeostasis is an emerging issue in dermatology to improve the current therapy for skin disorders, and the EGFR inhibitor-associated skin toxicities. Besides, controlling of keratinocyte stem cells by modulating the EGF receptor/ligand system assures advances in regenerative medicine of the skin. We present an overview of the recent progress in the field of the EGF receptor/ligand system on skin homeostasis and regulation of keratinocyte stem cells.

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