title: p63 regulates an adhesion programme and cell survival in epithelial cells.
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 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.
authors.affiliation: Department of Cell Biology, Harvard Medical School, 240 Longwood Ave, Boston, MA 02115, USA.
authors.forename: Danielle K
authors.initials: DK
authors.lastname: Carroll
authors.forename: Jason S
authors.initials: JS
authors.lastname: Carroll
authors.forename: Chee-Onn
authors.initials: CO
authors.lastname: Leong
authors.forename: Fang
authors.initials: F
authors.lastname: Cheng
authors.forename: Myles
authors.initials: M
authors.lastname: Brown
authors.forename: Alea A
authors.initials: AA
authors.lastname: Mills
authors.forename: Joan S
authors.initials: JS
authors.lastname: Brugge
authors.forename: Leif W
authors.initials: LW
authors.lastname: Ellisen
mesh_terms: 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
chemical_list: C081876:CKAP4 protein, human; D008565:Membrane Proteins; D020033:Protein Isoforms