The histone deacetylases HDAC1 and HDAC2 are required for the growth and survival of renal carcinoma cells

Archives of Toxicology
Nicole KiwelerOliver H Krämer

Abstract

Novel therapies are required for the treatment of metastatic renal cell carcinoma (RCC), which is associated with inoperable disease and patient death. Histone deacetylases (HDACs) are epigenetic modifiers and potential drug targets. Additional information on molecular pathways that are altered by histone deacetylase inhibitors (HDACi) in RCC cells is warranted. It should equally be delineated further which individual members of the 18 mammalian HDACs determine the survival and tumor-associated gene expression programs of such cells. Most importantly, an ongoing dispute whether HDACi promote or suppress metastasis-associated epithelial-to-mesenchymal transition (EMT) has to be resolved before HDACi are considered further as clinically relevant drugs. Here we show how HDACi affect murine and primary human RCC cells. We find that these agents induce morphological alterations resembling the metastasis-associated EMT. However, individual and proteomics-based analyses of epithelial and mesenchymal marker proteins and of EMT-associated transcription factors (EMT-TFs) reveal that HDACi do not trigger EMT. Pathway deconvolution analysis identifies reduced proliferation and apoptosis induction as key effects of HDACi. Furthermore, these...Continue Reading

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Citations

Jan 30, 2019·Cancers·Anna WawruszakAndrzej Stepulak
Jan 15, 2020·Journal of Cancer Research and Clinical Oncology·Nicole KiwelerOliver H Krämer
May 20, 2020·Expert Review of Proteomics·Francesca Raimondo, Marina Pitto
Jun 17, 2020·Experimental and Therapeutic Medicine·Huiwu LiLing Liu
Jul 1, 2020·Journal of Cellular and Molecular Medicine·Jiajun ZhouChaoqing Gao
Jan 8, 2019·F1000Research·Ellen G JarredPatrick S Western
Nov 30, 2019·Analytical Cellular Pathology (Amsterdam)·Monica NeaguMarieta Costache
Dec 17, 2020·Journal of Cellular and Molecular Medicine·Zhi-Peng QiPing-Hong Zhou
Jan 6, 2021·Clinical and Experimental Nephrology·Hongbing Liu
Mar 5, 2020·Seminars in Nephrology·David C Yang, Ching-Hsien Chen
Apr 3, 2021·Expert Review of Anticancer Therapy·Martina SpisarováHana Študentová
Jun 9, 2021·Journal of Experimental & Clinical Cancer Research : CR·Revati SharmaNuzhat Ahmed
Jun 11, 2021·European Journal of Medicinal Chemistry·Muhamad MustafaGamal El-Din A Abuo-Rahma

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Methods Mentioned

BETA
acetylation
confocal microscopy
light microscopy
proteomics assay
nuclear translocation
flow cytometry
transfection

Software Mentioned

R
R package “
GraphPad
Olympus Cell ^ A
GraphPad Prism
ENSEMBL
[UNK]
R package “ GOstats ”
Maxquant
BiomaRt

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