The transcription factor ZEB1 (δEF1) represses Plakophilin 3 during human cancer progression

被引：85

作者：

Aigner, Kirsten

Descovich, Luise

Mikula, Mario

Sultan, Aneesa

Dampier, Brigitta

Bonne, Stefan

van Roy, Frans

Mikulits, Wolfgang

Schreiber, Martin

Brabletz, Thomas

Sommergruber, Wolfgang

Schweifer, Norbert

Wernitznig, Andreas

Beug, Hartmut

Foisner, Roland

Eger, Andreas

机构：

[1] Med Univ Vienna, Dept Med Biochem, Max F Perutz Labs, A-1030 Vienna, Austria

[2] Med Univ Vienna, Dept Med 1, A-1030 Vienna, Austria

[3] Med Univ Vienna, Canc Res Inst, A-1030 Vienna, Austria

[4] Med Univ Vienna, Dept Obstet & Gynecol, A-1030 Vienna, Austria

[5] VIB, Dept Mol Biomed Res, Mol Cell Biol Uni, Ghent, Belgium

[6] Univ Ghent, B-9000 Ghent, Belgium

[7] Univ Freiburg, Dept Visceral & Gen Surg, Freiburg, Germany

[8] Boehringer Ingelheim Austria, Vienna, Austria

[9] Res Inst Mol Pathol, IMP, A-1030 Vienna, Austria

来源：

FEBS LETTERS | 2007年 / 581卷 / 08期

基金：

奥地利科学基金会;

关键词：

epithelial to mesenchymal transition; invasion; transcription; desmosomes; cell adhesion;

D O I：

10.1016/j.febslet.2007.03.026

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Plakophilin 3 (PKP3) belongs to the p120ctn family of armadillo-related proteins predominantly functioning in desmosome formation. Here we report that PKP3 is transcriptionally repressed by the F-cadherin repressor ZEB1 in metastatic cancer cells. ZEB1 physically associates with two conserved E-box elements in the PKP3 promoter and partially represses the activity of corresponding human and mouse PKP3 promoter fragments in reporter gene assays. In human tumours ZEB1 is upregulated in invasive cancer cells at the tumour-host interface, which is accompanied by downregulation of PKP3 expression levels. Hence, the transcriptional repression of PKP3 by ZEB1 contributes to ZEB1-mediated disintegration of intercellular adhesion and epithelial to mesenchymal transition. (c) 2007 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.

引用

页码：1617 / 1624

页数：8

共 32 条

[1] Defining desmosomal plakophilin-3 interactions [J].