p63: a crucial player in epithelial stemness regulation.

Yanan Li, Sara Giovannini, Tingting Wang, Jiankai Fang, Peishan Li, Changshun Shao, Ying Wang, Yufang Shi, Eleonora Candi, Gerry Melino, Francesca Bernassola

Journal: Oncogene 2023;42(46):3371-3384

PMID: 37848625

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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.

Address: Department of Experimental Medicine, TOR, University of Rome Tor Vergata, 00133, Rome, Italy.; The Third Affiliated Hospital of Soochow University, Institutes for Translational Medicine, Soochow University, Suzhou, 215000, China.; Department of Experimental Medicine, TOR, University of Rome Tor Vergata, 00133, Rome, Italy.; The Third Affiliated Hospital of Soochow University, Institutes for Translational Medicine, Soochow University, Suzhou, 215000, China.; Shanghai Institute of Nutrition and Health, Shanghai, 200031, China.; The Third Affiliated Hospital of Soochow University, Institutes for Translational Medicine, Soochow University, Suzhou, 215000, China. [email protected].; Department of Experimental Medicine, TOR, University of Rome Tor Vergata, 00133, Rome, Italy. [email protected].; Biochemistry Laboratory, Istituto Dermopatico Immacolata (IDI-IRCCS), 00100, Rome, Italy. [email protected].; Department of Experimental Medicine, TOR, University of Rome Tor Vergata, 00133, Rome, Italy. [email protected].; Department of Experimental Medicine, TOR, University of Rome Tor Vergata, 00133, Rome, Italy. [email protected].

DOI: 10.1038/s41388-023-02859-4