Histone Deacetylase Inhibitors and Phenotypical Transformation of Cancer Cells.
Anna WawruszakJoanna KalafutEstera OkonJakub CzapinskiMarta HalasaAlicja PrzybyszewskaPaulina MiziakKarolina OklaAdolfo Rivero-MullerAndrzej StepulakPublished in: Cancers (2019)
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.
Keyphrases
- epithelial mesenchymal transition
- histone deacetylase
- transforming growth factor
- signaling pathway
- clinical trial
- endothelial cells
- stem cells
- gene expression
- randomized controlled trial
- combination therapy
- high resolution
- cell proliferation
- young adults
- climate change
- risk assessment
- mass spectrometry
- induced pluripotent stem cells
- childhood cancer