Preprint Review Version 1 Preserved in Portico This version is not peer-reviewed

Long-Lived Epidermal Cancer-Initiating Cells

Version 1 : Received: 12 May 2017 / Approved: 12 May 2017 / Online: 12 May 2017 (18:15:31 CEST)

A peer-reviewed article of this Preprint also exists.

Youssef, M.; Cuddihy, A.; Darido, C. Long-Lived Epidermal Cancer-Initiating Cells. Int. J. Mol. Sci. 2017, 18, 1369. Youssef, M.; Cuddihy, A.; Darido, C. Long-Lived Epidermal Cancer-Initiating Cells. Int. J. Mol. Sci. 2017, 18, 1369.


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. Although primary prevention is possible through minimising sunlight exposure, the World Health Organisation estimates that between 2 and 3 million new cases of NMSCs are diagnosed each year, accounting for 1 in 3 of all newly diagnosed cancers. Furthermore, studies have estimated there has been a 2-fold increase in the incidence of NMSCs between 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 urgent. NMSCs are generally thought to arise from specific types of stem cells that become the source of clonal expansion of tumourigenic cells. Previous research on SCC has alluded to these stem cells being localised 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. More recent research has suggested that commitment to differentiation, which requires exiting the basal, progenitor-cell compartment, is a reversible mechanism. Genetic modifications engage differentiated cells into dedifferentiation, converting them into cancer-initiating cells (CICs) and thereby promoting a tumourigenic environment. Here we explore the most recent developments in the understanding of skin SCC cell of origin, and discuss a case study illustrating the loss of the Grainy-head like 3 (GRHL3) transcription factor in suprabasal layers, which confers a tendency towards tumour development and thereby challenging the “stem cell” theory of tumourigenesis.


squamous cell carcinoma (SCC), Grainyhead-like 3 (Grhl3), interfollicular epidermis (IFE), supra-basal epidermis, involucrin (IVL), cancer-initiating cell (CIC), cancer stem cell (CSC).


Medicine and Pharmacology, Oncology and Oncogenics

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