Article

p63 regulates an adhesion programme and cell survival in epithelial cells

Department of Cell Biology, Harvard Medical School, 240 Longwood Ave, Boston, MA 02115, USA.
Nature Cell Biology (Impact Factor: 20.06). 05/2006; 8(6):551-561. DOI: 10.1038/ncb1420
Source: PubMed

ABSTRACT p63 is critical for epithelial development yet little is known about the transcriptional programmes it regulates. By characterising transcriptional changes and cellular effects following modulation of p63 expression, we have defined a vital role for p63 in cellular adhesion. Knockdown of p63 expression caused downregulation of cell adhesion-associated genes, cell detachment and anoikis in mammary epithelial cells and keratinocytes. Conversely, overexpression of the TAp63 or Np63 isoforms of p63 upregulated cell adhesion molecules, increased cellular adhesion and conferred resistance to anoikis. Apoptosis induced by loss of p63 was rescued by signalling downstream of 4 integrin. Our results implicate p63 as a key regulator of cellular adhesion and survival in basal cells of the mammary gland and other stratified epithelial tissues.

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Available from: Chee-Onn Leong, Jun 23, 2014
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    • "Downregulation of ΔNp63 in Lbh-deficient MaSCs could be responsible for a range of phenotypes observed in our model. ΔNp63 controls stem cell self-renewal and quiescence, and promotes basal epithelial characteristics by regulating transcription of genes involved in cell proliferation, adhesion and the basal cytoskeleton, including K5 (Carroll et al., 2006; Romano et al., 2009; Wu et al., 2003; Yalcin-Ozuysal et al., 2010), which we found to be induced by LBH in HC11. By modulating LBH and p63 expression in established MEC culture systems, we demonstrate that LBH induces ΔNp63 at the mRNA level and that ΔNp63, indeed, acts downstream of LBH in promoting stemness and basal K5 expression. "
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    • "Published microarray data from human non-transformed MCF10A breast epithelial cells (Carroll et al., 2006) were re-analyzed for possible regulation of apoptosis-related genes by ∆Np63. shRNA against the p63 DNA-binding domain (DBD) was used to knock down all p63 isoforms (top), whereas shRNA against the p63 TA domain was TAp63-specific (bottom). "
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    • "While miR- 574-3p and miR-720 regulate p63 expression, iASPP KD does not exactly phenocopy p63 KD (Carroll et al, 2006; Truong et al, 2006). Indeed, while iASPP-depleted keratinocytes show a decrease of b1 integrin and an increase of a3 integrin expression without modifications of b4 integrin; p63 knockdown induces a strong decrease in the expression of b1, b4 and a3 integrins at mRNA level (Carroll et al, 2006). In addition, iASPP KD impairs cell proliferation similarly as p63 KD, but also induces a premature differentiation of skin equivalent, which is inhibited upon p63 silencing (Truong et al, 2006), suggesting that iASPP may regulate other signalling pathways in addition of p63. "
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