title: Interplay between KLF4 and ZEB2/SIP1 in the regulation of E-cadherin expression.
abstract: 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.
authors: Laboratory of Molecular Oncology, GIGA cancer, Liège University, B34, 4000 Liège, Belgium. benjamin.koopmansch@student.ulg.ac.be
authors: Benjamin
authors: B
authors: Koopmansch
authors: Geert
authors: G
authors: Berx
authors: Jean-Michel
authors: JM
authors: Foidart
authors: Christine
authors: C
authors: Gilles
authors: Rosita
authors: R
authors: Winkler
mesh_terms: D015703:Antigens, CD; D001667:Binding, Competitive; D015820:Cadherins / Q000235:genetics*; D045744:Cell Line, Tumor; D047369:Chromatin Immunoprecipitation; D058750:Epithelial-Mesenchymal Transition / Q000235:genetics; D015972:Gene Expression Regulation, Neoplastic; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D000090062:Kruppel-Like Factor 4; D051741:Kruppel-Like Transcription Factors / Q000378:metabolism*; D011401:Promoter Regions, Genetic; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism*; D015533:Transcriptional Activation; D000074165:Zinc Finger E-box Binding Homeobox 2
chemical_list: D015703:Antigens, CD; C513384:CDH1 protein, human; D015820:Cadherins; D018398:Homeodomain Proteins; C000715467:KLF4 protein, human; D000090062:Kruppel-Like Factor 4; D051741:Kruppel-Like Transcription Factors; D012097:Repressor Proteins; C492363:ZEB2 protein, human; D000074165:Zinc Finger E-box Binding Homeobox 2