Medizinische Universität Graz Austria/Österreich - Forschungsportal - Medical University of Graz
Gewählte Publikation:
SHR Neuro Krebs Kardio Lipid Stoffw Microb
Wels, C; Joshi, S; Koefinger, P; Bergler, H; Schaider, H.
Transcriptional Activation of ZEB1 by Slug Leads to Cooperative Regulation of the Epithelial-Mesenchymal Transition-Like Phenotype in Melanoma
J INVEST DERMATOL. 2011; 131(9): 1877-1885.
Doi: 10.1038/jid.2011.142
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- Führende Autor*innen der Med Uni Graz
- Schaider Helmut
- Wels Christian
- Co-Autor*innen der Med Uni Graz
- Joshi Shripad Prakash
- Köfinger Petra
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- Abstract:
- The E-box-binding zinc finger transcription factors Slug and ZEB1 are important repressors of E-cadherin, contributing to epithelial-mesenchymal transition (EMT) in primary epithelial cancers. Activator or repressor status of EMT transcription factors defines consequences for tumorigenesis. We show that changes in expression levels of Slug in melanoma cell lines lead to concomitant alterations of ZEB1 expression. Electrophoretic mobility shift, luciferase reporter, and chromatin immunoprecipitation assays identified Slug as a direct transcriptional activator at E-boxes of the ZEB1 promoter. Transcriptional activation of ZEB1 was demonstrated to be specific for Slug, as EMT regulators Snail and Twist failed to influence ZEB1 expression. Slug and ZEB1 cooperatively repressed E-cadherin expression resulting in decreased adhesion to human keratinocytes, but promoted migration of melanoma cells. Our results show that the transcriptional activity of ZEB1 is increased by Slug, suggesting a hierarchical organized expression of EMT transcription factors through directed activation, triggering an EMT-like process in melanoma.
- Find related publications in this database (using NLM MeSH Indexing)
- Cadherins - genetics
- Cell Adhesion - physiology
- Cell Line, Tumor -
- Cell Movement - physiology
- Epithelial-Mesenchymal Transition - physiology
- Fibroblasts - cytology
- Gene Expression Regulation, Neoplastic - physiology
- Homeodomain Proteins - genetics
- Humans -
- Keratinocytes - cytology
- Melanoma - pathology
- Phenotype -
- Promoter Regions, Genetic - physiology
- RNA, Small Interfering - pharmacology
- Skin Neoplasms - pathology
- Transcription Factors - genetics
- Transcriptional Activation - physiology
- Twist Transcription Factor - metabolism