Tiwari, N. and Meyer-Schaller, N. and Arnold, P. and Antoniadis, H. and Pachkov, M. and van Nimwegen, E. and Christofori, G.. (2013) Klf4 is a transcriptional regulator of genes critical for EMT, including Jnk1 (Mapk8). PLoS one, Vol. 8, H. 2 , e57329.
Full text not available from this repository.
Official URL: http://edoc.unibas.ch/dok/A6124437
Downloads: Statistics Overview
Abstract
We have identified the zinc-finger transcription factor Kruppel-like factor 4 (Klf4) among the transcription factors that are significantly downregulated in their expression during epithelial-mesenchymal transition (EMT) in mammary epithelial cells and in breast cancer cells. Loss and gain of function experiments demonstrate that the down-regulation of Klf4 expression is required for the induction of EMT and for metastasis . In addition, reduced Klf4 expression correlates with shorter disease-free survival of subsets of breast cancer patients. Yet, reduced expression of Klf4 also induces apoptosis in cells undergoing TGFβ-induced EMT. Chromatin immunoprecipitation/deep-sequencing in combination with gene expression profiling reveals direct Klf4 target genes, including E-cadherin (), N-cadherin (), vimentin (), β-catenin (), VEGF-A (), endothelin-1 () and Jnk1 (). Thereby, Klf4 acts as a transcriptional activator of epithelial genes and as a repressor of mesenchymal genes. Specifically, increased expression of Jnk1 () upon down-regulation of its transcriptional repressor Klf4 is required for EMT cell migration and for the induction of apoptosis. The data demonstrate a central role of Klf4 in the maintenance of epithelial cell differentiation and the prevention of EMT and metastasis.
Faculties and Departments: | 05 Faculty of Science > Departement Biozentrum > Computational & Systems Biology > Bioinformatics (van Nimwegen) 03 Faculty of Medicine > Departement Biomedizin > Former Units at DBM > Tumor Biology (Christofori) |
---|---|
UniBasel Contributors: | van Nimwegen, Erik and Christofori, Gerhard M. |
Item Type: | Article, refereed |
Article Subtype: | Research Article |
Publisher: | Public Library of Science |
ISSN: | 1932-6203 |
Note: | Publication type according to Uni Basel Research Database: Journal article |
Related URLs: | |
Identification Number: |
|
Last Modified: | 10 Apr 2015 09:13 |
Deposited On: | 24 May 2013 09:19 |
Repository Staff Only: item control page