The Transcriptional factor ZEB1 represses Syndecan 1 expression in prostate cancer

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  • dc.contributor.author Farfán, Nancy
  • dc.contributor.author Ocarez, Nallatt
  • dc.contributor.author Castellón, Enrique A.
  • dc.contributor.author Mejía, Nilo
  • dc.contributor.author García de Herreros, Antonio
  • dc.contributor.author Contreras, Héctor R.
  • dc.date.accessioned 2018-11-19T09:19:17Z
  • dc.date.available 2018-11-19T09:19:17Z
  • dc.date.issued 2018
  • dc.description.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.
  • dc.description.sponsorship 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).
  • dc.format.mimetype application/pdf
  • dc.identifier.citation Farfán N, Ocarez N, Castellón EA, Mejía N, de Herreros AG, Contreras HR. The Transcriptional factor ZEB1 represses Syndecan 1 expression in prostate cancer. Sci Rep. 2018;8(1):11467. DOI: 10.1038/s41598-018-29829-1
  • dc.identifier.doi http://dx.doi.org/10.1038/s41598-018-29829-1
  • dc.identifier.issn 2045-2322
  • dc.identifier.uri http://hdl.handle.net/10230/35786
  • dc.language.iso eng
  • dc.publisher Nature Publishing Group
  • dc.relation.ispartof Scientific Reports. 2018;8(1):11467
  • dc.relation.projectID info:eu-repo/grantAgreement/ES/1PE/SAF2016-76461-R
  • dc.rights © The Author(s) 2018. This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
  • dc.rights.accessRights info:eu-repo/semantics/openAccess
  • dc.rights.uri http://creativecommons.org/licenses/by/4.0/
  • dc.subject.keyword Cancer
  • dc.subject.keyword Cell adhesion
  • dc.title The Transcriptional factor ZEB1 represses Syndecan 1 expression in prostate cancer
  • dc.type info:eu-repo/semantics/article
  • dc.type.version info:eu-repo/semantics/publishedVersion

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