p63 regulates an adhesion programme and cell survival in epithelial cells

被引:359
作者
Carroll, Danielle K.
Carroll, Jason S.
Leong, Chee-Onn
Cheng, Fang
Brown, Myles
Mills, Alea. A.
Brugge, Joan S.
Ellisen, Leif W.
机构
[1] Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA 02115 USA
[2] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA
[3] Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA
[4] Harvard Univ, Sch Med, Boston, MA 02114 USA
[5] NYU, Courant Inst Math Sci, Bioinformat Grp, New York, NY 10003 USA
[6] NYU, Dept Biol, New York, NY 10003 USA
[7] Cold Spring Harbor Lab, Cold Spring Harbor, NY 11724 USA
关键词
D O I
10.1038/ncb1420
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
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 gamma or Delta Np63 alpha 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 beta 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.
引用
收藏
页码:551 / 561
页数:11
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