Maintaining Epithelial Stemness with P63

In stratified epithelial and glandular tissues, homeostasis relies on the self-renewing capacity of stem cells, which are within the basal layer. The p53 family member p63 is an indispensable transcription factor for epithelial morphogenesis and stemness. A splice variant of the transcription factor p63 that lacks an amino-terminal domain, ΔNp63, is selectively found in the basal compartments of several ectoderm-derived tissues such as stratified and glandular epithelia, in which it is required for the replenishment of stem cells. Thus far, the transcriptional programs downstream of p63 in stemness regulation remain incompletely defined. Unveiling the molecular basis of stem cell self-renewal may be relevant in understanding how this process may contribute to cancer development. In this review, we specifically highlight experimental investigations, which suggest that p63 is a marker of normal epithelial stem cells and describe p63 transcriptional targets that may be involved in stemness regulation. Finally, we discuss relevant findings implicating p63 in epithelial cancer stem cell biology.