Data from ZEB1 Collaborates with ELK3 to Repress E-Cadherin Expression in Triple-Negative Breast Cancer Cells

Abstract

<div>Abstract<p>ZEB1 has intrinsic oncogenic functions that control the epithelial-to-mesenchymal transition (EMT) of cancer cells, impacting tumorigenesis from its earliest stages. By integrating microenvironment signals and being implicated in feedback regulatory loops, ZEB1 appears to be a central switch that determines EMT and metastasis of cancer cells. Here, we found that ZEB1 collaborates with ELK3, a ternary complex factor belonging to the ETS family, to repress <i>E-cadherin</i> expression. ZEB1 functions as a transcriptional activator of <i>ELK3</i>. We first identified that <i>ELK3</i> and <i>ZEB1</i> have a positively correlated expression in breast cancer cells by using multiple databases for correlation analysis. Molecular analysis revealed that ZEB1 functions as a transcriptional activator of <i>ELK3</i> expression. GST pull-down assay and coimmunoprecipitation analysis of wild-type or domain deletion mutants of ZEB1 and ELK3 showed that these 2 proteins directly bound each other. Furthermore, we demonstrated that ZEB1 and ELK3 collaborate to repress the expression of <i>E-cadherin</i>, a representative protein that initiates EMT. Our finding suggested that ELK3 is a novel factor of the ZEB1/E-cadherin axis in triple-negative breast cancer cells.</p>Implications:<p>ELK3 is a novel factor in the ZEB1/E-cadherin axis and ZEB1 has a dual role in ELK3 as a transcriptional activator and as a collaborator to repress <i>E-cadherin</i> expression in triple-negative breast cancer cells.</p></div>