ArticlePloS one2016
A Histone Deacetylase Inhibitor Suppresses Epithelial-Mesenchymal Transition and Attenuates Chemoresistance in Biliary Tract Cancer.
Article in PloS one, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers.
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Who cites it
32 citing papers in PubMed, 59 citations in OpenAlex.
- Endothelial to mesenchymal transition in cardiovascular diseases: molecular insights and clinical perspectives.European heart journal · 2026Review
- Identification, functional insights and therapeutic targeting of EMT tumour states.Nature reviews. Cancer · 2026Review
- Review
- Targeting histone deacetylase-3 blocked epithelial-mesenchymal plasticity and metastatic dissemination in gastric cancer.Cell biology and toxicology · 2023Article
- ACAT-1-Regulated Cholesteryl Ester Accumulation Modulates Gemcitabine Resistance in Biliary Tract Cancer.Annals of surgical oncology · 2022Article
- Review
- Review
- Histone deacetylase 1 facilitates aerobic glycolysis and growth of endometrial cancer.Oncology letters · 2021Article
- Silver Nanoparticles Modulate the Epithelial-to-Mesenchymal Transition in Estrogen-Dependent Breast Cancer Cells In Vitro.International journal of molecular sciences · 2021Article
- HDAC Screening Identifies the HDAC Class I Inhibitor Romidepsin as a Promising Epigenetic Drug for Biliary Tract Cancer.Cancers · 2021Article
- Acetylation of KLF5 maintains EMT and tumorigenicity to cause chemoresistant bone metastasis in prostate cancer.Nature communications · 2021Article
- Heterogeneity of Treg/Th17 According to Cancer Progression and Modification in Biliary Tract Cancers via Self-Producing Cytokines.Digestive diseases and sciences · 2020Article
- Small Ones to Fight a Big Problem-Intervention of Cancer Metastasis by Small Molecules.Cancers · 2020Review
- TGFB1-induced autophagy affects the pattern of pancreatic cancer progression in distinct ways depending on SMAD4 status.Autophagy · 2020Article
- Cancer Stem Cells as a Potential Target to Overcome Multidrug Resistance.Frontiers in oncology · 2020Review
- Metabolic Plasticity and Epithelial-Mesenchymal Transition.Journal of clinical medicine · 2019Review
- Implication for Cancer Stem Cells in Solid Cancer Chemo-Resistance: Promising Therapeutic Strategies Based on the Use of HDAC Inhibitors.Journal of clinical medicine · 2019Review
- The postoperative peak number of leukocytes after hepatectomy is a significant prognostic factor for cholangiocarcinoma.Molecular and clinical oncology · 2019Article
- Synergistic antitumour activity of HDAC inhibitor SAHA and EGFR inhibitor gefitinib in head and neck cancer: a key role for ΔNp63α.British journal of cancer · 2019Article
- Review
Corrections and comments
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Authors and funding
15 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Epithelial-mesenchymal transition (EMT) is involved in the characteristics of malignancy, such as invasion, metastasis, and chemoresistance. In biliary tract cancer (BTC), EMT is induced by transforming growth factor-beta 1 (TGF-β1). The EMT is reversible; therefore, it is conceivable that it could be related to some epigenetic changes. We focused on histone deacetylase (HDAC) inhibitors as regulators of TGF-β1 signaling, and investigated their effect on EMT and chemoresistance. We employed four BTC cell lines (MzChA-1, gemcitabine-resistant MzChA-1, TFK-1, and gemcitabine-resistant TFK-1) and used vorinostat as the HDAC inhibitor. The relative mRNA expression of an epithelial marker (CDH1) and mesenchymal markers (CDH2, vimentin, SNAI1) were measured by qRT-PCR to evaluate factors associated with EMT. MTT (3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay was performed to evaluate the chemoresistance of each cell line. In addition, NOD/SCID mice were used to evaluate the effect of vorinostat in vivo. In the parent MzChA-1 and TFK-1 cell lines, TGF-β1 induced EMT and chemoresistance; while vorinostat inhibited the EMT and chemoresistance induced by TGF-β1. In gemcitabine-resistant cell lines that highly expressed TGF-β1, vorinostat inhibited EMT and attenuated chemoresistance. We showed that vorinostat inhibits nuclear translocation of SMAD4 which is a signaling factor of TGF-β1, and this is one of the mechanisms by which vorinostat regulates EMT. We also showed that vorinostat attenuates the binding affinity of SMAD4 to the CDH1-related transcription factors SNAI1, SNAI2, ZEB1, ZEB2, and TWIST. Furthermore, combination therapy with vorinostat and gemcitabine improved survival time in the mice xenografted with gemcitabine resistant MzChA-1 cells. In conclusion, vorinostat regulated TGF-β1-induced EMT and chemoresistance through inhibition of SMAD4 nuclear translocation.
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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.