Abstract
Epithelial-mesenchymal Transition (EMT) is a de-differentiation process in which epithelial cells lose their epithelial properties to acquire mesenchymal features. EMT is essential for embryogenesis and wound healing but is aberrantly activated in pathological conditions like fibrosis and cancer. Tumor-associated EMT contributes to cancer cell initiation, invasion, metastasis, drug resistance and recurrence. This dynamic and reversible event is governed by EMT-transcription factors (EMT-TFs) with epigenetic complexes. In this review, we discuss recent advances regarding the mechanisms that modulate EMT in the context of epigenetic regulation, with emphasis on epigenetic drugs, such as DNA demethylating reagents, inhibitors of histone modifiers and non-coding RNA medication. Therapeutic contributions that improve epigenetic regulation of EMT will translate the clinical manifestation as treating cancer progression more efficiently.
Highlights
Epithelial-mesenchymal transition (EMT) is a phenomenon which involves the capacity of cells to interconvert between cellular states of the epithelial-mesenchymal axis and varying biological requirements (Bhatia et al, 2017; Yang et al, 2020)
Outside mediators trigger within epithelial cells a large number of intracellular cascades, which refashion expressions of several EMTTFs such as Snail/Slug, ZEB1/2 and Twist1/2 (Puisieux et al, 2014)
A notable molecular hallmark of Epithelial-mesenchymal Transition (EMT) is Epigenetic Drugs in Cancer Metastasis repression of E-cadherin, a transmembrane glycoprotein encoded by the epithelial marker gene CDH1 and essential for epithelial cell-cell junctions
Summary
Epithelial-mesenchymal transition (EMT) is a phenomenon which involves the capacity of cells to interconvert between cellular states of the epithelial-mesenchymal axis and varying biological requirements (Bhatia et al, 2017; Yang et al, 2020). MBDs interact with transcription factors, which recruit chromatin remodelers and histone-modifying proteins, thereby turning DNA methylation into activation or repressive signal depending on the cellular context. P300/CBP-associated factor (PCAF)-dependent acetylation of the transcription factor intestine-specific homeobox (ISX) promotes its interaction with BRD4 and translocation of the resulting complex into the nucleus This complex binds to promoters of EMT genes, where acetylation of histone three at lysine 9, 14, and 18 initiates transcriptional activation; these findings indicate that the p300/CBP-ISX-BRD4 axis mediates EMT and regulates tumor initiation and metastasis (Wang L.-T. et al, 2020). HDAC inhibitors induce mesenchymal transition of the colon carcinoma cells, especially in the presence of TGF-β1 (Ji et al, 2015) They enhance invasion of human melanoma cells via upregulation of N-cadherin and inhibition of RhoA activity (Díaz-Núñez et al, 2016), and these inhibitors upregulate Snail through AKT/GSK-3β signals and post-transcriptional modification to promote EMT in colorectal cancer cells (Feng et al, 2015). HDAC inhibitors emerge as a promising class of drug, in combination with other agents
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