HDAC5 Expression in Urothelial Carcinoma Cell Lines Inhibits Long-Term Proliferation but Can Promote Epithelial-to-Mesenchymal Transition
Class I histone deacetylases (HDACs) generally promote cell proliferation and tumorigenesis, whereas class IIA HDACs like HDAC4 and HDAC5 may promote or impede cancer development in a tissue-dependent manner. In urothelial carcinoma (UC), HDAC5 is often downregulated. Accordingly, HDAC5 was weakly e...
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doaj-429c0a2185594fb5ae37b753db0bf81e2020-11-25T00:52:58ZengMDPI AGInternational Journal of Molecular Sciences1422-00672019-04-01209213510.3390/ijms20092135ijms20092135HDAC5 Expression in Urothelial Carcinoma Cell Lines Inhibits Long-Term Proliferation but Can Promote Epithelial-to-Mesenchymal TransitionAnanda Ayyappan Jaguva Vasudevan0Michèle J. Hoffmann1Michael L. C. Beck2Gereon Poschmann3Patrick Petzsch4Constanze Wiek5Kai Stühler6Karl Köhrer7Wolfgang A. Schulz8Günter Niegisch9Department of Urology, Medical Faculty, Heinrich Heine University Düsseldorf, 40225 Düsseldorf, GermanyDepartment of Urology, Medical Faculty, Heinrich Heine University Düsseldorf, 40225 Düsseldorf, GermanyDepartment of Urology, Medical Faculty, Heinrich Heine University Düsseldorf, 40225 Düsseldorf, GermanyInstitute for Molecular Medicine, University Hospital Düsseldorf, 40225 Düsseldorf, GermanyBiological and Medical Research Centre (BMFZ), Heinrich Heine University Düsseldorf, 40225 Düsseldorf, GermanyDepartment of Otolaryngology, Medical Faculty, Heinrich Heine University Düsseldorf, 40225 Düsseldorf, GermanyInstitute for Molecular Medicine, University Hospital Düsseldorf, 40225 Düsseldorf, GermanyBiological and Medical Research Centre (BMFZ), Heinrich Heine University Düsseldorf, 40225 Düsseldorf, GermanyDepartment of Urology, Medical Faculty, Heinrich Heine University Düsseldorf, 40225 Düsseldorf, GermanyDepartment of Urology, Medical Faculty, Heinrich Heine University Düsseldorf, 40225 Düsseldorf, GermanyClass I histone deacetylases (HDACs) generally promote cell proliferation and tumorigenesis, whereas class IIA HDACs like HDAC4 and HDAC5 may promote or impede cancer development in a tissue-dependent manner. In urothelial carcinoma (UC), HDAC5 is often downregulated. Accordingly, HDAC5 was weakly expressed in UC cell lines suggesting a possible tumor-suppressive function. We therefore characterized the effects of stable HDAC5 expression in four UC cell lines (RT112, VM-Cub-1, SW1710 and UM-UC-3) with different phenotypes reflecting the heterogeneity of UC, by assessing proliferation, clonogenicity and migration ability. Further, we detailed changes in the proteome and transcriptome by immunoblotting, mass spectrometry and RNA sequencing analysis. We observed that HDAC5 overexpression in general decreased cell proliferation, but in one cell line (VM-Cub-1) induced a dramatic change from an epitheloid to a mesenchymal phenotype, i.e., epithelial-mesenchymal transition (EMT). These phenotypical changes were confirmed by comprehensive proteomics and transcriptomics analyses. In contrast to HDAC5, overexpression of HDAC4 exerted only weak effects on cell proliferation and phenotypes. We conclude that overexpression of HDAC5 may generally decrease proliferation in UC, but, intriguingly, may induce EMT on its own in certain circumstances.https://www.mdpi.com/1422-0067/20/9/2135histone deacetylasebladder cancerHDAC4HDAC5transcriptomicsproteomicsEMTepigeneticsTGFβTNFα |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Ananda Ayyappan Jaguva Vasudevan Michèle J. Hoffmann Michael L. C. Beck Gereon Poschmann Patrick Petzsch Constanze Wiek Kai Stühler Karl Köhrer Wolfgang A. Schulz Günter Niegisch |
spellingShingle |
Ananda Ayyappan Jaguva Vasudevan Michèle J. Hoffmann Michael L. C. Beck Gereon Poschmann Patrick Petzsch Constanze Wiek Kai Stühler Karl Köhrer Wolfgang A. Schulz Günter Niegisch HDAC5 Expression in Urothelial Carcinoma Cell Lines Inhibits Long-Term Proliferation but Can Promote Epithelial-to-Mesenchymal Transition International Journal of Molecular Sciences histone deacetylase bladder cancer HDAC4 HDAC5 transcriptomics proteomics EMT epigenetics TGFβ TNFα |
author_facet |
Ananda Ayyappan Jaguva Vasudevan Michèle J. Hoffmann Michael L. C. Beck Gereon Poschmann Patrick Petzsch Constanze Wiek Kai Stühler Karl Köhrer Wolfgang A. Schulz Günter Niegisch |
author_sort |
Ananda Ayyappan Jaguva Vasudevan |
title |
HDAC5 Expression in Urothelial Carcinoma Cell Lines Inhibits Long-Term Proliferation but Can Promote Epithelial-to-Mesenchymal Transition |
title_short |
HDAC5 Expression in Urothelial Carcinoma Cell Lines Inhibits Long-Term Proliferation but Can Promote Epithelial-to-Mesenchymal Transition |
title_full |
HDAC5 Expression in Urothelial Carcinoma Cell Lines Inhibits Long-Term Proliferation but Can Promote Epithelial-to-Mesenchymal Transition |
title_fullStr |
HDAC5 Expression in Urothelial Carcinoma Cell Lines Inhibits Long-Term Proliferation but Can Promote Epithelial-to-Mesenchymal Transition |
title_full_unstemmed |
HDAC5 Expression in Urothelial Carcinoma Cell Lines Inhibits Long-Term Proliferation but Can Promote Epithelial-to-Mesenchymal Transition |
title_sort |
hdac5 expression in urothelial carcinoma cell lines inhibits long-term proliferation but can promote epithelial-to-mesenchymal transition |
publisher |
MDPI AG |
series |
International Journal of Molecular Sciences |
issn |
1422-0067 |
publishDate |
2019-04-01 |
description |
Class I histone deacetylases (HDACs) generally promote cell proliferation and tumorigenesis, whereas class IIA HDACs like HDAC4 and HDAC5 may promote or impede cancer development in a tissue-dependent manner. In urothelial carcinoma (UC), HDAC5 is often downregulated. Accordingly, HDAC5 was weakly expressed in UC cell lines suggesting a possible tumor-suppressive function. We therefore characterized the effects of stable HDAC5 expression in four UC cell lines (RT112, VM-Cub-1, SW1710 and UM-UC-3) with different phenotypes reflecting the heterogeneity of UC, by assessing proliferation, clonogenicity and migration ability. Further, we detailed changes in the proteome and transcriptome by immunoblotting, mass spectrometry and RNA sequencing analysis. We observed that HDAC5 overexpression in general decreased cell proliferation, but in one cell line (VM-Cub-1) induced a dramatic change from an epitheloid to a mesenchymal phenotype, i.e., epithelial-mesenchymal transition (EMT). These phenotypical changes were confirmed by comprehensive proteomics and transcriptomics analyses. In contrast to HDAC5, overexpression of HDAC4 exerted only weak effects on cell proliferation and phenotypes. We conclude that overexpression of HDAC5 may generally decrease proliferation in UC, but, intriguingly, may induce EMT on its own in certain circumstances. |
topic |
histone deacetylase bladder cancer HDAC4 HDAC5 transcriptomics proteomics EMT epigenetics TGFβ TNFα |
url |
https://www.mdpi.com/1422-0067/20/9/2135 |
work_keys_str_mv |
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