Abstract
Histone deacetylase inhibitors (HDIs) are a group of potent epigenetic drugs which have been investigated for their therapeutic potential in various clinical disorders, including hematological malignancies and solid tumors. Currently, several HDIs are already in clinical use and many more are on clinical trials. HDIs have shown efficacy to inhibit initiation and progression of cancer cells. Nevertheless, both pro-invasive and anti-invasive activities of HDIs have been reported, questioning their impact in carcinogenesis. The aim of this review is to compile and discuss the most recent findings on the effect of HDIs on the epithelial-mesenchymal transition (EMT) process in human cancers. We have summarized the impact of HDIs on epithelial (E-cadherin, β-catenin) and mesenchymal (N-cadherin, vimentin) markers, EMT activators (TWIST, SNAIL, SLUG, SMAD, ZEB), as well as morphology, migration and invasion potential of cancer cells. We further discuss the use of HDIs as monotherapy or in combination with existing or novel anti-neoplastic drugs in relation to changes in EMT.
Highlights
Epithelial-mesenchymal transition (EMT) is a biological reversible process in which cells undergo multiple biochemical changes—lose their epithelial properties, including cell-cell adhesion and cell polarity, and acquire mesenchymal phenotype, including the ability to invade the extracellular matrix (ECM) and potentially migrate to the distant places
HDAC1, HDAC2, HDAC9, HDAC10, SIRT3, SIRT5, SIRT6, SIRT7 is present in 100% of patients with breast cancer
The results revealed that the morphological changes were similar pursuing Trochostatin A (TSA) or VPA with or without TGF-β1 co-treatment
Summary
Epithelial-mesenchymal transition (EMT) is a biological reversible process in which cells undergo multiple biochemical changes—lose their epithelial properties, including cell-cell adhesion and cell polarity, and acquire mesenchymal phenotype, including the ability to invade the extracellular matrix (ECM) and potentially migrate to the distant places. Induction of EMT includes reorganization of cytoskeleton proteins, activation of transcription factors and production of extracellular matrix-degrading enzymes [1,2]. Recent studies revealed the large role of epigenetic mechanisms including DNA methylation, chromatin rearrangement, histone modifications and non-coding RNAs in the initiation and progression of cancers [3]. Cancers 2019, 11, x modulators, which regulation controls phenotypic transformation. Abnormaland histone modification patterns roles in gene expression via changes in chromatic structure recruitment of epigenetic are closely associated with numerous diseases including cancers, they are considered promising modulators, which controls phenotypic transformation. Abnormal histone modification patterns biomarkers [4]
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