The Transcriptional factor ZEB1 represses Syndecan 1 expression in prostate cancer
| Autor: | Nilo Mejía, Enrique A. Castellón, Antonio García de Herreros, Héctor R. Contreras, Nancy Farfán, Nallatt Ocarez |
|---|---|
| Předmět: |
0301 basic medicine
Male Epithelial-Mesenchymal Transition Transcription Genetic Slug Repressor lcsh:Medicine Article Syndecan 1 Epigenesis Genetic Small hairpin RNA 03 medical and health sciences Cell Line Tumor Gene expression Cell Adhesion Humans Epithelial–mesenchymal transition Promoter Regions Genetic lcsh:Science Cancer Regulation of gene expression Multidisciplinary biology lcsh:R Prostatic Neoplasms Zinc Finger E-box-Binding Homeobox 1 Cell adhesion biology.organism_classification Cell biology carbohydrates (lipids) Gene Expression Regulation Neoplastic 030104 developmental biology PC-3 Cells Ectopic expression lcsh:Q Snail Family Transcription Factors Syndecan-1 Transcription Factors |
| Zdroj: | Recercat. Dipósit de la Recerca de Catalunya instname Scientific Reports, Vol 8, Iss 1, Pp 1-14 (2018) Scientific Reports Artículos CONICYT CONICYT Chile instacron:CONICYT |
| Popis: | Syndecan 1 (SDC-1) is a cell surface proteoglycan with a significant role in cell adhesion, maintaining epithelial integrity. SDC1 expression is inversely related to aggressiveness in prostate cancer (PCa). During epithelial to mesenchymal transition (EMT), loss of epithelial markers is mediated by transcriptional repressors such as SNAIL, SLUG, or ZEB1/2 that bind to E-box promoter sequences of specific genes. The effect of these repressors on SDC-1 expression remains unknown. Here, we demonstrated that SNAIL, SLUG and ZEB1 expressions are increased in advanced PCa, contrarily to SDC-1. SNAIL, SLUG and ZEB1 also showed an inversion to SDC-1 in prostate cell lines. ZEB1, but not SNAIL or SLUG, represses SDC-1 as demonstrated by experiments of ectopic expression in epithelial prostate cell lines. Inversely, expression of ZEB1 shRNA in PCa cell line increased SDC-1 expression. The effect of ZEB1 is transcriptional since ectopic expression of this gene represses SDC-1 promoter activity and ZEB1 binds to the SDC-1 promoter as detected by ChIP assays. An epigenetic mark associated to transcription repression H3K27me3 was bound to the same sites that ZEB1. In conclusion, this study identifies ZEB1 as a key repressor of SDC-1 during PCa progression and point to ZEB1 as a potentially diagnostic marker for PCa. This work was supported by the following grants: FONDECYT N° 1110269 and 1151214 (HRC), FONDECYT N° 1140417 (EAC), Agencia Estatal de Investigación (AEI) and Fondo Europeo de Desarrollo Regional-FEDER (SAF2016-76461-R) (AGH). MECESUP scholarship, CONICYT scholarship N° 21140772 and the Scholarship for short residencies of the University of Chile (2014). |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|