p63: a crucial player in epithelial stemness regulation

Oncogene. 2023 Nov;42(46):3371-3384. doi: 10.1038/s41388-023-02859-4. Epub 2023 Oct 17.


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.

Publication types

  • Review

MeSH terms

  • Epithelium / metabolism
  • Humans
  • Neoplasms* / genetics
  • Neoplasms* / metabolism
  • Phosphoproteins / genetics
  • Protein Isoforms / metabolism
  • Transcription Factors / genetics
  • Transcription Factors / metabolism
  • Tumor Suppressor Proteins* / metabolism


  • Tumor Suppressor Proteins
  • Transcription Factors
  • Protein Isoforms
  • Phosphoproteins