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Sci Rep. 2018 Jul 31;8(1):11467. doi: 10.1038/s41598-018-29829-1.

The transcriptional factor ZEB1 represses Syndecan 1 expression in prostate cancer.

Author information

1
Department of Basic and Clinic Oncology, Faculty of Medicine, University of Chile, Santiago, Chile.
2
Institute of Agricultural Research (INIA-Chile), La Platina Research Centre, Av. Santa Rosa 11, 610, P.O. Box 439-3, Santiago, Chile.
3
Programa de Recerca en Càncer, Institut Hospital del Mar d'Investigacions Mèdiques (IMIM), Barcelona, Spain.
4
Departament de Ciències Experimentals i de la Salut, Universitat Pompeu Fabra, Barcelona, Spain.
5
Department of Basic and Clinic Oncology, Faculty of Medicine, University of Chile, Santiago, Chile. hcontrer@med.uchile.cl.

Abstract

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.

PMID:
30065348
PMCID:
PMC6068163
DOI:
10.1038/s41598-018-29829-1
[Indexed for MEDLINE]
Free PMC Article

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