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Int. J. Mol. Sci. 2017, 18(7), 1369; doi:10.3390/ijms18071369

Long-Lived Epidermal Cancer-Initiating Cells

1
Department of Medicine, Monash University Central Clinical School, Prahran, VIC 3004, Australia
2
Division of Cancer Research, Peter MacCallum Cancer Centre, Grattan Street, Parkville, VIC 3052, Australia
3
Sir Peter MacCallum Department of Oncology, The University of Melbourne, Melbourne, VIC 3052, Australia
*
Author to whom correspondence should be addressed.
Received: 12 May 2017 / Revised: 15 June 2017 / Accepted: 21 June 2017 / Published: 27 June 2017
(This article belongs to the Special Issue Molecular Research of Epidermal Stem Cells 2017)
View Full-Text   |   Download PDF [1030 KB, uploaded 27 June 2017]   |  

Abstract

Non-melanomatous skin cancers (NMSCs), which include basal and squamous cell carcinoma (BCC and SCC respectively), represent a significant burden on the population, as well as an economic load to the health care system; yet treatments of these preventable cancers remain ineffective. Studies estimate that there has been a 2-fold increase in the incidence of NMSCs between the 1960s and 1980s. The increase in cases of NMSCs, as well as the lack of effective treatments, makes the need for novel therapeutic approaches all the more necessary. To rationally develop more targeted treatments for NMSCs, a better understanding of the cell of origin, in addition to the underlying pathophysiological mechanisms that govern the development of these cancers, is urgently required. Research over the past few years has provided data supporting both a “bottom up” and “top down” mechanism of tumourigenesis. The “bottom up” concept involves a cancer stem cell originating in the basal compartment of the skin, which ordinarily houses the progenitor cells that contribute towards wound healing and normal cell turnover of overlying epidermal skin layers. The “top down” concept involves a more differentiated cell undergoing genetic modifications leading to dedifferentiation, giving rise to cancer initiating cells (CICs). This review explores both concepts, to paint a picture of the skin SCC cell of origin, the underlying biology, and also how this knowledge might be exploited to develop novel therapies. View Full-Text
Keywords: squamous cell carcinoma (SCC); Grainyhead-like 3 (Grhl3); interfollicular epidermis (IFE); supra-basal epidermis; Involucrin (IVL); cancer-initiating cell (CIC); cancer stem cell (CSC) squamous cell carcinoma (SCC); Grainyhead-like 3 (Grhl3); interfollicular epidermis (IFE); supra-basal epidermis; Involucrin (IVL); cancer-initiating cell (CIC); cancer stem cell (CSC)
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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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Youssef, M.; Cuddihy, A.; Darido, C. Long-Lived Epidermal Cancer-Initiating Cells. Int. J. Mol. Sci. 2017, 18, 1369.

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