p63 regulates an adhesion programme and cell survival in epithelial cells.
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 TAp63gamma or deltaNp63alpha 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 beta4 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.
Carroll
Danielle K
DK
Department of Cell Biology, Harvard Medical School, 240 Longwood Ave, Boston, MA 02115, USA.
Carroll
Jason S
JS
Leong
Chee-Onn
CO
Cheng
Fang
F
Brown
Myles
M
Mills
Alea A
AA
Brugge
Joan S
JS
Ellisen
Leif W
LW
D023102:Anoikis; D002448:Cell Adhesion / Q000235:genetics; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000235:genetics; D004847:Epithelial Cells / Q000166:cytology*; D005786:Gene Expression Regulation; D006801:Humans; D015603:Keratinocytes / Q000166:cytology; D008565:Membrane Proteins / Q000235:genetics / Q000502:physiology*; D020033:Protein Isoforms
C081876:CKAP4 protein, human; D008565:Membrane Proteins; D020033:Protein Isoforms