Oncogenic Ras: A double-edged sword for human epidermal stem and transient amplifying cells.
The human epidermal clonal evolution, i.e. the transition from stem cells (SCs) to transient amplifying (TA)-cells and post-mitotic cells, is a continuous and tightly regulated process that ensures physiologic tissue homeostasis. The Ras family of small GTPases has a key role in skin homeostasis and tumorigenesis. Indeed, activating mutations in Ras genes have been found in human cutaneous squamous cell carcinomas (cSCCs) and in experimentally-induced murine cSCCs. In mouse models, the Ras signaling might lead to hyperproliferative phenotypes, including the development of cSCCs, depending on the nature of the founding cells. Tumor-initiating cells or Cancer Stem Cells (CSCs) have been demonstrated in murine and human cSCCs even if the mechanism of their development from normal SCs or TA-cells is not completely elucidated. Here, the relation between the Ras expression outcome and the clonogenic potential of the target keratinocyte is discussed.
a Vascular Pathology Laboratory, Fondazione Luigi Maria Monti, IDI-IRCCS , Rome , Italy.
Elena
E
Dellambra
D000818:Animals; D063646:Carcinogenesis; D004817:Epidermis / Q000473:pathology*; D006706:Homeostasis; D006801:Humans; D014411:Neoplastic Stem Cells / Q000473:pathology*; D012878:Skin Neoplasms / Q000201:enzymology / Q000473:pathology; D018631:ras Proteins / Q000378:metabolism*
D018631:ras Proteins
Bmi-1; Ras; cutaneous squamous cell carcinoma; human; keratinocytes; p16INK4a; p63; primary cultures; stem cells