Breast Cancer Research and Treatment

, Volume 143, Issue 1, pp 99–111 | Cite as

Histone deacetylase inhibitor entinostat reverses epithelial to mesenchymal transition of breast cancer cells by reversing the repression of E-cadherin

  • Preeti Shah
  • Yael Gau
  • Gauri Sabnis
Preclinical study


Loss of ERα in breast cancer correlates with poor prognosis, increased recurrence rates, and higher incidence of metastasis. Epigenetic silencing of E-cadherin (loss of which is associated with more invasive phenotype) is observed in metastatic cell lines and invasive breast cancers. Here, we are showing that entinostat (ENT) can reverse epithelial to mesenchymal transition (EMT), which is considered to be a first step in the process of metastases formation. Triple-negative breast cancer cells such as MDA-MB-231 and Hs578T show a basal phenotype characterized by loss of E-cadherin expression and higher expression of mesenchymal markers such as N-cadherin and vimentin along with transcriptional repressors such as twist and snail. When MDA-MB-231 and Hs578T cells or tumors were treated with ENT, E-cadherin transcription was increased along with reduction in N-cadherin mRNA expression. Chromatin immunoprecipitation assay showed that treatment of MDA-MB-231 and Hs578T cells increased the activation of E-cadherin promoter by reducing the association of twist and snail with the E-cadherin (CDH1) promoter and downregulated both the snail and twist. ENT also inhibited cell migration in vitro. In addition, phosphorylation of vimentin was increased, as well as remodeling of vimentin filaments. ENT treatment also reduced formation of tubulin-based microtentacles, which help floating cells attach to other surfaces. These findings suggest that ENT can reverse EMT and may reduce the formation of metastasis.


Epithelial to mesenchymal transition E-cadherin HDAC inhibitor 



Estrogen receptor


Aromatase inhibitors


Histone deacetylase inhibitors







This work was supported by Grants to G Sabnis (KG10037) from Susan G Komen for the Cure.

Conflict of interest

We do not have any relevant conflict of interest. Syndax Pharmaceuticals (MA, USA) provided entinostat and letrozole used in this study.

Supplementary material

10549_2013_2784_MOESM1_ESM.pdf (951 kb)
Supplementary material 1 (PDF 950 kb)
10549_2013_2784_MOESM2_ESM.docx (149 kb)
Supplementary material 2 (DOCX 149 kb)


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Copyright information

© Springer Science+Business Media New York 2013

Authors and Affiliations

  1. 1.Department of Pharmacology and Experimental TherapeuticsUniversity of Maryland School of MedicineBaltimoreUSA

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