Carroll Danielle K, Carroll Jason S, Leong Chee-Onn, Cheng Fang, Brown Myles, Mills Alea A, Brugge Joan S, Ellisen Leif W
Department of Cell Biology, Harvard Medical School, 240 Longwood Ave, Boston, MA 02115, USA.
Nat Cell Biol. 2006 Jun;8(6):551-61. doi: 10.1038/ncb1420. Epub 2006 May 21.
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.
p63对上皮发育至关重要，但对其调控的转录程序却知之甚少。通过对p63表达调控后的转录变化和细胞效应进行表征，我们确定了p63在细胞黏附中的重要作用。p63表达的敲低导致乳腺上皮细胞和角质形成细胞中细胞黏附相关基因的下调、细胞脱离和失巢凋亡。相反，p63的TAp63γ或ΔNp63α亚型的过表达上调了细胞黏附分子，增加了细胞黏附并赋予了对失巢凋亡的抗性。β4整合素下游信号传导挽救了因p63缺失诱导的细胞凋亡。我们的结果表明p63是乳腺和其他复层上皮组织基底细胞中细胞黏附和存活的关键调节因子。
