Article abstract
Nature Cell Biology 8, 551 - 561 (2006)
Published online: 21 May 2006 | doi:10.1038/ncb1420
p63 regulates an adhesion programme and cell survival in epithelial cells
Danielle K. Carroll1, Jason S. Carroll2, Chee-Onn Leong3, Fang Cheng1,4, Myles Brown2, Alea. A. Mills5, Joan S. Brugge1 & Leif W. Ellisen3
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.
- Department of Cell Biology, Harvard Medical School, 240 Longwood Ave, Boston, MA 02115, USA.
- Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, 44 Binney St, Boston, MA 02115, USA.
- Massachusetts General Hospital Cancer Center and Harvard Medical School, Boston, MA 02114, USA.
- Bioinformatics Group, Courant Institute of Mathematics and Department of Biology, New York University, New York City, NY 10003, USA.
- Cold Spring Harbor Laboratory, Cold Spring Harbor, NY 11724, USA.
Correspondence to: Joan S. Brugge1 e-mail: joan_brugge@hms.harvard.edu
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