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Int. J. Mol. Sci. 2017, 18(7), 1591; doi:10.3390/ijms18071591

The Role of p16INK4a Pathway in Human Epidermal Stem Cell Self-Renewal, Aging and Cancer

1
Laboratory of Vascular Pathology, Istituto Dermopatico dell'Immacolata, Istituto di Ricovero e Cura a Carattere Scientifico (IDI-IRCCS), Fondazione Luigi Maria Monti (FLMM), via Monti di Creta 104, 00167 Rome, Italy
2
Molecular and Cell Biology Laboratory, Istituto Dermopatico dell'Immacolata, Istituto di Ricovero e Cura a Carattere Scientifico (IDI-IRCCS), Fondazione Luigi Maria Monti (FLMM), via Monti di Creta 104, 00167 Rome, Italy
*
Author to whom correspondence should be addressed.
Received: 27 June 2017 / Revised: 13 July 2017 / Accepted: 19 July 2017 / Published: 22 July 2017
(This article belongs to the Special Issue Molecular Research of Epidermal Stem Cells 2017)
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Abstract

The epidermis is a self-renewing tissue. The balance between proliferation and differentiation processes is tightly regulated to ensure the maintenance of the stem cell (SC) population in the epidermis during life. Aging and cancer may be considered related endpoints of accumulating damages within epidermal self-renewing compartment. p16INK4a is a potent inhibitor of the G1/S-phase transition of the cell cycle. p16INK4a governs the processes of SC self-renewal in several tissues and its deregulation may result in aging or tumor development. Keratinocytes are equipped with several epigenetic enzymes and transcription factors that shape the gene expression signatures of different epidermal layers and allow dynamic and coordinated expression changes to finely balance keratinocyte self-renewal and differentiation. These factors converge their activity in the basal layer to repress p16INK4a expression, protecting cells from senescence, and preserving epidermal homeostasis and regeneration. Several stress stimuli may activate p16INK4a expression that orchestrates cell cycle exit and senescence response. In the present review, we discuss the role of p16INK4a regulators in human epidermal SC self-renewal, aging and cancer. View Full-Text
Keywords: human keratinocytes; p16INK4a; epidermal stem cells; skin aging; non-melanoma skin cancers human keratinocytes; p16INK4a; epidermal stem cells; skin aging; non-melanoma skin cancers
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

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D’Arcangelo, D.; Tinaburri, L.; Dellambra, E. The Role of p16INK4a Pathway in Human Epidermal Stem Cell Self-Renewal, Aging and Cancer. Int. J. Mol. Sci. 2017, 18, 1591.

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