p63: a crucial player in epithelial stemness regulation
Yanan Li, Sara Giovannini, Tingting Wang, Jiankai Fang, Peishan Li, Changshun Shao, Ying Wang, Massimiliano Agostini, Pierluigi Bove, Alessandro Mauriello, Giuseppe Novelli, Mauro Piacentini, Valentina Rovella, Manuel Scimeca, Giuseppe Sica, Qiang Sun, Giuseppe Tisone, Yufang Shi, Eleonora Candi, Gerry Melino, Francesca Bernassola
Abstract
Epithelial tissue homeostasis is closely associated with the self-renewal and differentiation behaviors of epithelial stem cells (ESCs). p63, a well-known marker of ESCs, is an indispensable factor for their biological activities during epithelial development. The diversity of p63 isoforms expressed in distinct tissues allows this transcription factor to have a wide array of effects. p63 coordinates the transcription of genes involved in cell survival, stem cell self-renewal, migration, differentiation, and epithelial-to-mesenchymal transition. Through the regulation of these biological processes, p63 contributes to, not only normal epithelial development, but also epithelium-derived cancer pathogenesis. In this review, we provide an overview of the role of p63 in epithelial stemness regulation, including self-renewal, differentiation, proliferation, and senescence. We describe the differential expression of TAp63 and ΔNp63 isoforms and their distinct functional activities in normal epithelial tissues and in epithelium-derived tumors. Furthermore, we summarize the signaling cascades modulating the TAp63 and ΔNp63 isoforms as well as their downstream pathways in stemness regulation.