Maintaining epithelial stemness with p63

Abstract

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.

Personalized Stem Cell Therapy to Correct Corneal Defects Due to a Unique Homozygous-Heterozygous Mosaicism of Ectrodactyly-Ectodermal Dysplasia-Clefting Syndrome

“…In sharp contrast, tissues generated from R279H and R304Q-p63 OMESCs showed defects in both stratification and differentiation, thus resulting in severe tissue hypoplasia and lack of proper tissue polarity (Fig. 4D), consistent with previous reports [28][29][30][31][32][33][34][35]. Collectively, these results strongly support the potential clinical use of p.R311K-p63 HHs for the development of CAOMESCs, to reconstruct the ocular surface of this unique case of EEC syndrome.…”

Vascular ageing and endothelial cell senescence: Molecular mechanisms of physiology and diseases

“…The complex balance between p53 family and HIF can impact on mitochondrial activity and redox cellular status; this might indirectly affect cellular senescence and ageing. Kim et al, 2014;Melino et al, 2015;Memmi et al, 2015;Rufini et al, 2012;Su et al, 2009;Tyner et al, 2002). All three models develop kyphosis, alopecia, premature thinning of the skin.…”

ΔNp63α Acts as a Lineage-Survival Oncogene in Squamous Cell Carcinoma

“…In view of our observation that ΔNp63α overexpressing epidermis contains more C34-positive stem cells, promotion of stem cell division or suppression of stem cell differentiation are the two most plausible mechanisms at work in our model. The molecular pathways implicating p63 in epithelial cancer stem cell maintenance have been thoroughly reviewed by Melino and colleagues [1].…”

“…Of the multiple isoforms found in higher vertebrates, ΔNp63α is the predominant one expressed in the epidermis. Lacking the N-terminal, but containing the C-terminal transactivation domain, ΔNp63α has both transcriptional repressor and transactivation properties, positively and negatively regulating a plethora of genes, involved in proliferation, stemness, cell death, inflammation and differentiation [1].…”

“…Of the multiple isoforms found in higher vertebrates, ΔNp63α is the predominant one expressed in the epidermis. Lacking the N-terminal, but containing the C-terminal transactivation domain, ΔNp63α has both transcriptional repressor and transactivation properties, positively and negatively regulating a plethora of genes, involved in proliferation, stemness, cell death, inflammation and differentiation [1].Two decades following the discovery of TP63, ΔNp63α has been proven to be a crucial player in Squamous Cell Carcinoma (SCC) development and treatment. Particularly because the majority of SCCs overexpress ΔNp63α, often as a result of amplification of the TP63 genomic region [2,3].…”