A joint study between the groups of Valeria Poli and Enzo Calautti demonstrates that a moderate but sustained increase of STAT3 activity enhances epidermal stem cell properties, delays differentiation and favors spontaneous immortalization of keratinocyte

Skin tumorigenesis is enhanced by overexpression in keratinocytes of the constitutively active STAT3C mutant, which also induces robust, psoriasis-like epidermal hyperplasia. In this paper published in Experimental Dermatology http://www.ncbi.nlm.nih.gov/pubmed/25382846, Valeria Orecchia, Gabriella Regis and colleagues demonstrated that STAT3C expression at physiological levels in knock-in mice leads to mild epidermal hyperplasia and attenuated expression of terminal differentiation markers. This correlates with enhanced proliferative and clonogenic potential, attenuated senescence and, strikingly, high frequency spontaneous immortalization. These results suggest that moderate levels of continuous STAT3 activation, which mimic chronic inflammatory conditions, may establish a pre-neoplastic state in part by promoting the escape of epidermal progenitor cells from differentiation and senescence checkpoints.