ArticleJournal of neuro-oncology2009
Reactivation of death receptor 4 (DR4) expression sensitizes medulloblastoma cell lines to TRAIL.
Article in Journal of neuro-oncology, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
What it found
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The trial behind it
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Who cites it
24 citing papers in PubMed, 49 citations in OpenAlex.
- Ionizing Radiation Increases Death Receptor 5 (DR5)-Mediated Cell Death, but Not Death Receptor 4 (DR4)-Mediated Cell Death in 3D Tumor Spheroids.International journal of molecular sciences · 2025Article
- The pivotal role of irradiation-induced apoptosis in the pathogenesis and therapy of medulloblastoma.Cancer reports (Hoboken, N.J.) · 2024Review
- Apoptosis evasion via long non-coding RNAs in colorectal cancer.Cancer cell international · 2022Review
- Targeting the apoptosis pathway to treat tumours of the paediatric nervous system.Cell death & disease · 2022Review
- Epigenetic Deregulation of Apoptosis in Cancers.Cancers · 2021Review
- Histone deacetylase inhibitors induce medulloblastoma cell death independent of HDACs recruited in REST repression complexes.Molecular genetics & genomic medicine · 2020Article
- Review
- p53 at the Crossroads between Different Types of HDAC Inhibitor-Mediated Cancer Cell Death.International journal of molecular sciences · 2019Review
- Epigenetic Targeting of Autophagy via HDAC Inhibition in Tumor Cells: Role of p53.International journal of molecular sciences · 2018Review
- KDM2B, an H3K36-specific demethylase, regulates apoptotic response of GBM cells to TRAIL.Cell death & disease · 2017Article
- Thymoquinone inhibits growth of human medulloblastoma cells by inducing oxidative stress and caspase-dependent apoptosis while suppressing NF-κB signaling and IL-8 expression.Molecular and cellular biochemistry · 2016Article
- Trailing TRAIL Resistance: Novel Targets for TRAIL Sensitization in Cancer Cells.Frontiers in oncology · 2015Review
- Medulloblastoma development: tumor biology informs treatment decisions.CNS oncology · 2015Review
- Histone deacetylases: a saga of perturbed acetylation homeostasis in cancer.The journal of histochemistry and cytochemistry : official journal of the Histochemistry Society · 2014Review
- Real-time imaging of the dynamics of death receptors and therapeutics that overcome TRAIL resistance in tumors.Oncogene · 2013Article
- The deubiquitylase USP37 links REST to the control of p27 stability and cell proliferation.Oncogene · 2013Article
- Deregulated chromatin remodeling in the pathobiology of brain tumors.Neuromolecular medicine · 2013Review
- Histone deacetylase inhibitors sensitize glioblastoma cells to TRAIL-induced apoptosis by c-myc-mediated downregulation of cFLIP.Oncogene · 2012Article
- REST is a novel prognostic factor and therapeutic target for medulloblastoma.Molecular cancer therapeutics · 2012Article
- Article
Corrections and comments
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Authors and funding
11 authors at 3 institutions in 3 countries.
Funding
Abstract
objectApoptosis, a key cellular response to therapeutic agents is often inactivated in tumor cells. In this study, we evaluated the expression of the tumor necrosis family of death receptors, DR4 and DR5, in medulloblastoma tumor samples and cell lines to determine if epigenetic modulation of gene expression could sensitize tumor cell lines to TRAIL-mediated apoptosis.
methodsHuman medulloblastoma samples and cell lines were analyzed for DR4 and DR5 expression by quantitative PCR and immunofluorescence assays. Cell lines with downregulated expression of one or both genes were treated with the histone deacetylase inhibitor, MS-275, and the expression of DR4 and DR5 measured by quantitative PCR, Western blotting, flow cytometry and chromatin immunoprecipitation assays. Induction of apoptosis in the presence of MS-275 was evaluated by TUNEL assay and its ability to augment TRAIL-mediated cytotoxicity was determined by MTT assays, Western blotting and flow cytometry.
resultsCompared to normal cerebellum, DR4, but not DR5 expression was consistently downregulated in medulloblastoma tumor samples and in Daoy and D283 cell lines. Interestingly, MS-275 decreased cell growth and induced apoptosis in Daoy and D283 cells. In Daoy cells, this coincided with increased histone H3 and H4 acetylation at the DR4 promoter and enhanced DR4 gene and protein expression as well as elevated Caspase-8 activity. The involvement of DR4 in the cellular response to MS-275 was further confirmed by the observation that knockdown of DR4 and FADD abrogated apoptosis. Further, addition of TRAIL to MS-275 treated cells resulted in an enhancement of apoptosis, suggesting that the upregulated death receptors were functional.
conclusionOur study provides an understanding of the role of DR4 in apoptosis of medulloblastoma cell lines and suggests a potential contribution of aberrant histone deacetylation to the resistance of medulloblastoma cells to therapeutic death.
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