Interplay between KLF4 and ZEB2/SIP1 in the regulation of E-cadherin expression.

[en] E-cadherin expression is repressed by ZEB2/SIP1 while it is induced by KLF4. Independent data from the literature indicate that these two transcription factors could bind close to each other in the proximal region of the E-cadherin gene promoter. We have here explored a potential competition between ZEB2 and KLF4 for the binding to the E-cadherin promoter. We show an inverse correlation between ZEB2 expression levels and KLF4 recruitment on the E-cadherin promoter in three breast cancer cell lines and in A431/HA.ZEB2 cells in which ZEB2 expression is induced by doxycycline (DOX). We identified a region of the E-cadherin promoter bound by KLF4 which is necessary for the activation of the E-cadherin promoter activity after KLF4 overexpression. This region is localized between positions -28 and -10 and thus overlaps with one of the ZEB2 binding sites. Deleting the bipartite ZEB2 binding site results in increased KLF4 induced E-cadherin promoter activity. Taken together, our results suggest that E-cadherin expression in cancer cells is controlled by a balance between ZEB2 and KLF4 expression levels.

Disciplines :

Biochemistry, biophysics & molecular biology

Author, co-author :

Koopmansch, Benjamin

Berx, Geert; Ghent University > Department for Molecular Biomedical Research, > Unit of Molecular and Cellular Oncology,

Foidart, Jean-Michel ; Université de Liège - ULiège > Département des sciences cliniques > Gynécologie - Obstétrique

Gilles, Christine ; Université de Liège - ULiège > Département des sciences cliniques > Labo de biologie des tumeurs et du développement

Winkler, Rose ; Université de Liège - ULiège > Département des sciences biomédicales et précliniques > Anatomie et cytologie pathologiques

Language :

English

Title :

Interplay between KLF4 and ZEB2/SIP1 in the regulation of E-cadherin expression.

Publication date :

22 February 2013

Journal title :

Biochemical and Biophysical Research Communications

ISSN :

0006-291X

eISSN :

1090-2104

Publisher :

Academic Press, San Diego, United States - California

Volume :

431

Issue :

Pages :

652

Peer reviewed :

Peer reviewed

Commentary :

Available on ORBi :

since 14 February 2013

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