p63 is known to have a crucial role in epithelial development, but little is known about the downstream pathways that are involved. However, reporting in Nature Cell Biology, Carroll, Brugge, Ellisen and colleagues now describe how, by characterizing the transcriptional and cellular changes that occur following the modulation of p63 expression, they have identified an essential role for p63 in the regulation of epithelial cell adhesion and survival.
These authors have ... defined a role for p63 as a crucial regulator of epithelial cell adhesion.
The human breast epithelial cell line MCF-10A was used as a model system to study the roles of p63 in epithelial biology. There are several distinct isoforms of p63, so the authors first investigated their relative importance in MCF-10A cells by specifically disrupting them using short hairpin RNAs (shRNAs). The specific loss of the 
Np63
isoform resulted in cell rounding, detachment and apoptosis, an effect that could be blocked by the expression of an shRNA-insensitive mutant of Np63. This finding indicates that Np63 is essential for MCF-10A cell survival.
Carroll and co-workers then compared the changes in gene expression that follow the loss or gain of p63 function to elucidate how p63 loss causes cell detachment. They found that many cell-adhesion-associated genes showed reduced expression when p63 was downregulated and increased expression when p63 was overexpressed, and these changes strongly correlated with the protein levels of integrins and extracellular matrix proteins. So, p63 seems to have a role in regulating cell-adhesion programmes, in particular, those involved in cell–matrix adhesion.
The apoptosis that is induced by the loss of p63 could be rescued by the constitutive expression of 
4 integrin, a signalling protein that is involved in matrix-induced survival and is regulated by p63. Furthermore, it was shown that p63 also regulates cell adhesion in primary mammary cells and keratinocytes. These authors have therefore provided a preliminary understanding of the pathways that are downstream of p63 and defined a role for p63 as a crucial regulator of epithelial cell adhesion.
ORIGINAL RESEARCH PAPER
- Carroll, D. K. et al. p63 regulates an adhesion programme and cell survival in epithelial cells. Nature Cell Biol. 8, 551–561 (2006) | Article |
FURTHER READING
- Fuchs, E. & Raghavan, S. Getting under the skin of epidermal morphogenesis. Nature Rev. Genet. 3, 199–209 (2002) | Article |