Interplay between KLF4 and ZEB2/SIP1 in the regulation of E-cadherin expression
Interplay between KLF4 and ZEB2/SIP1 in the regulation of E-cadherin expression
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DOI：
10.1016/j.bbrc.2013.01.070
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发表时间：
2013-02-22
影响因子：
3.1
通讯作者：
Winkler, Rosita
中科院分区：
文献类型：
--
作者：
Koopmansch, Benjamin;Berx, Geert;Winkler, Rosita
ZEB2/SIP1可抑制E-cadherin的表达，而KLF4可诱导E-cadherin表达。文献中的独立数据表明，这两个转录因子可以在E-cadherin基因启动子的近端区域相互结合。我们在这里探索了ZEB2和KLF4之间结合e -钙粘蛋白启动子的潜在竞争。我们发现在三种乳腺癌细胞系和A431/HA中，ZEB2表达水平与E-cadherin启动子上KLF4的募集呈负相关。强力霉素（DOX）诱导ZEB2表达的ZEB2细胞。我们发现了一个与KLF4结合的E-cadherin启动子区域，这是KLF4过表达后激活E-cadherin启动子活性所必需的。该区域位于28号和10号位点之间，因此与一个ZEB2结合位点重叠。删除两部分ZEB2结合位点导致KLF4诱导的E-cadherin启动子活性增加。综上所述，我们的研究结果表明，E-cadherin在癌细胞中的表达受到ZEB2和KLF4表达水平平衡的控制。(C) 2013爱思唯尔公司版权所有。
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 dose 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. (C) 2013 Elsevier Inc. All rights reserved.