ArticleCell death discovery2016
An epithelial marker promoter induction screen identifies histone deacetylase inhibitors to restore epithelial differentiation and abolishes anchorage independence growth in cancers.
Article in Cell death discovery, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
25 citing papers in PubMed, 47 citations in OpenAlex.
- Urothelial-lineage master transcription factor hub proteomics shows mechanisms impeding urothelial cancer cell differentiation.bioRxiv : the preprint server for biology · 2026Article
- Lack of SMARCB1 expression characterizes a subset of human and murine peripheral T-cell lymphomas.Nature communications · 2024Article
- HDAC1/2 control mesothelium/ovarian cancer adhesive interactions impacting on Talin-1-α5β1-integrin-mediated actin cytoskeleton and extracellular matrix protein remodeling.Journal of experimental & clinical cancer research : CR · 2024Article
- Recent Advances in Transcription Factors Biomarkers and Targeted Therapies Focusing on Epithelial-Mesenchymal Transition.Cancers · 2023Review
- Article
- Repression of the PRELP gene is relieved by histone deacetylase inhibitors through acetylation of histone H2B lysine 5 in bladder cancer.Clinical epigenetics · 2022Article
- 3D genome organization in the epithelial-mesenchymal transition spectrum.Genome biology · 2022Article
- Beyondcell: targeting cancer therapeutic heterogeneity in single-cell RNA-seq data.Genome medicine · 2021Article
- Review
- Cytostatic Action of Novel Histone Deacetylase Inhibitors in Androgen Receptor-Null Prostate Cancer Cells.Pharmaceuticals (Basel, Switzerland) · 2021Article
- Epithelial to Mesenchymal Transition: A Mechanism that Fuels Cancer Radio/Chemoresistance.Cells · 2020Review
- KRCC1: A potential therapeutic target in ovarian cancer.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2020Article
- Histone deacetylases, Mbd3/NuRD, and Tet2 hydroxylase are crucial regulators of epithelial-mesenchymal plasticity and tumor metastasis.Oncogene · 2020Article
- Inhibition of histone deacetylation rescues phenotype in a mouse model of Birk-Barel intellectual disability syndrome.Nature communications · 2020Article
- Ovarian Cancer Stem Cells: Role in Metastasis and Opportunity for Therapeutic Targeting.Cancers · 2019Review
- Revisiting Histone Deacetylases in Human Tumorigenesis: The Paradigm of Urothelial Bladder Cancer.International journal of molecular sciences · 2019Review
- Review
- Three-Component Repurposed Technology for Enhanced Expression: Highly Accumulable Transcriptional Activators via Branched Tag Arrays.The CRISPR journal · 2018Article
- Epigenetics in ovarian cancer: premise, properties, and perspectives.Molecular cancer · 2018Review
- HDAC1 inhibition by MS-275 in mesothelial cells limits cellular invasion and promotes MMT reversal.Scientific reports · 2018Article
Corrections and comments
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Authors and funding
9 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Epithelial-mesenchymal transition (EMT), a crucial mechanism in development, mediates aggressiveness during carcinoma progression and therapeutic refractoriness. The reversibility of EMT makes it an attractive strategy in designing novel therapeutic approaches. Therefore, drug discovery pipelines for EMT reversal are in need to discover emerging classes of compounds. Here, we outline a pre-clinical drug screening platform for EMT reversal that consists of three phases of drug discovery and validation. From the Phase 1 epithelial marker promoter induction (EpI) screen on a library consisting of compounds being approved by Food and Drug Administration (FDA), Vorinostat (SAHA), a histone deacetylase inhibitor (HDACi), is identified to exert EMT reversal effects by restoring the expression of an epithelial marker, E-cadherin. An expanded screen on 41 HDACi further identifies 28 compounds, such as class I-specific HDACi Mocetinosat, Entinostat and CI994, to restore E-cadherin and ErbB3 expressions in ovarian, pancreatic and bladder carcinoma cells. Mocetinostat is the most potent HDACi to restore epithelial differentiation with the lowest concentration required for 50% induction of epithelial promoter activity (EpIC-50).The HDACi exerts paradoxical effects on EMT transcriptional factors such as SNAI and ZEB family and the effects are context-dependent in epithelial- and mesenchymal-like cells. In vitro functional studies further show that HDACi induced significant increase in anoikis and decrease in spheroid formation in ovarian and bladder carcinoma cells with mesenchymal features. This study demonstrates a robust drug screening pipeline for the discovery of compounds capable of restoring epithelial differentiation that lead to significant functional lethality.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.