p63: a crucial player in epithelial stemness regulation
Patient pathways for rare diseases in Europe: ataxia as an example
17 October 2023
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Oncogene. 2023 Oct 17. doi: 10.1038/s41388-023-02859-4. Epub ahead of print. PMID: 37848625.

p63: a crucial player in epithelial stemness regulation

Authors: Yanan Li 1 2, Sara Giovannini 1, Tingting Wang 2, Jiankai Fang 2, Peishan Li 2, Changshun Shao 2, Ying Wang 3; TOR centre; Yufang Shi 4, Eleonora Candi 5 6, Gerry Melino 7, Francesca Bernassola 8

Affiliation:

  1. Department of Experimental Medicine, TOR, University of Rome Tor Vergata, 00133, Rome, Italy.
  2. The Third Affiliated Hospital of Soochow University, Institutes for Translational Medicine, Soochow University, Suzhou, 215000, China.
  3. Shanghai Institute of Nutrition and Health, Shanghai, 200031, China.
  4. 4
  5. The Third Affiliated Hospital of Soochow University, Institutes for Translational Medicine, Soochow University, Suzhou, 215000, China. yfshi@suda.edu.cn.
  6. Department of Experimental Medicine, TOR, University of Rome Tor Vergata, 00133, Rome, Italy. candi@uniroma2.it.
  7. Biochemistry Laboratory, Istituto Dermopatico Immacolata (IDI-IRCCS), 00100, Rome, Italy. candi@uniroma2.it.
  8. Department of Experimental Medicine, TOR, University of Rome Tor Vergata, 00133, Rome, Italy. melino@uniroma2.it.
  9. Department of Experimental Medicine, TOR, University of Rome Tor Vergata, 00133, Rome, Italy. bernasso@uniroma2.it.

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.

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