ArticleThe Journal of clinical investigation2020
Epigenetic modulator inhibition overcomes temozolomide chemoresistance and antagonizes tumor recurrence of glioblastoma.
Article in The Journal of clinical investigation, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 22 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.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
22 citing papers in PubMed, 36 citations in OpenAlex.
- Multi-responsive tetrahedral DNA frameworks forChemical science · 2026Article
- MBD3 deficiency decommissions the nucleosome remodeling and deacetylase complex and orchestrates the epigenetic regulation of gene expression to suppress neuroblastoma progression.Neuro-oncology · 2026Article
- Overcoming Chemoresistance in Glioblastoma: Mechanisms, Therapeutic Strategies, and Functional Precision Medicine.International journal of molecular sciences · 2026Review
- Bridging MBD3 functions in developmental biology and glioma heterogeneity to immune remodeling with future perspectives.Frontiers in immunology · 2026Review
- Canonical Wnt signaling regulates Mbd3 protein stability during neurogenesis.Experimental & molecular medicine · 2025Article
- Epigenetic Alterations in Glioblastoma Multiforme as Novel Therapeutic Targets: A Scoping Review.International journal of molecular sciences · 2025Article
- Overcoming temozolomide resistance in glioma: recent advances and mechanistic insights.Acta neuropathologica communications · 2025Review
- CD9 expression rivals IDH mutation as a prognostic marker in glioma: a novel nomogram approach.Frontiers in neurology · 2025Article
- MGMT activated by Wnt pathway promotes cisplatin tolerance through inducing slow-cycling cells and nonhomologous end joining in colorectal cancer.Journal of pharmaceutical analysis · 2024Article
- Role of glioma stem cells in promoting tumor chemo- and radioresistance: A systematic review of potential targeted treatments.World journal of stem cells · 2024Article
- MBD3 promotes epithelial-mesenchymal transition in gastric cancer cells by upregulating ACTG1 via the PI3K/AKT pathway.Biological procedures online · 2024Article
- Review
- Novel insights into histone lysine methyltransferases in cancer therapy: From epigenetic regulation to selective drugs.Journal of pharmaceutical analysis · 2023Review
- MBD3 promotes hepatocellular carcinoma progression and metastasis through negative regulation of tumour suppressor TFPI2.British journal of cancer · 2022Article
- RBBP4-p300 axis modulates expression of genes essential for cell survival and is a potential target for therapy in glioblastoma.Neuro-oncology · 2022Article
- Sox9 directs divergent epigenomic states in brain tumor subtypes.Proceedings of the National Academy of Sciences of the United States of America · 2022Article
- Inhibitory effects of temozolomide on glioma cells is sensitized by RSL3-induced ferroptosis but negatively correlated with expression of ferritin heavy chain 1 and ferritin light chain.Laboratory investigation; a journal of technical methods and pathology · 2022Article
- Modified Adenosines Sensitize Glioblastoma Cells to Temozolomide by Affecting DNA Methyltransferases.Frontiers in pharmacology · 2022Article
- Pyrvinium pamoate regulates MGMT expression through suppressing the Wnt/β-catenin signaling pathway to enhance the glioblastoma sensitivity to temozolomide.Cell death discovery · 2021Article
- Identification and characterization of N6-methyladenosine modification of circRNAs in glioblastoma.Journal of cellular and molecular medicine · 2021Article
Corrections and comments
- Erratum issued
Authors and funding
9 authors at 4 institutions in 3 countries.
Funding
Abstract
Glioblastoma multiforme (GBM) heterogeneity causes a greater number of deaths than any other brain tumor, despite the availability of alkylating chemotherapy. GBM stem-like cells (GSCs) contribute to GBM complexity and chemoresistance, but it remains challenging to identify and target GSCs or factors that control their activity. Here, we identified a specific GSC subset and show that activity of these cells is positively regulated by stabilization of methyl CpG binding domain 3 (MBD3) protein. MBD3 binds to CK1A and to BTRCP E3 ubiquitin ligase, triggering MBD3 degradation, suggesting that modulating this circuit could antagonize GBM recurrence. Accordingly, xenograft mice treated with the CK1A activator pyrvinium pamoate (Pyr-Pam) showed enhanced MBD3 degradation in cells expressing high levels of O6-methylguanine-DNA methyltransferase (MGMT) and in GSCs, overcoming temozolomide chemoresistance. Pyr-Pam blocked recruitment of MBD3 and the repressive nucleosome remodeling and deacetylase (NuRD) complex to neurogenesis-associated gene loci and increased acetyl-histone H3 activity and GSC differentiation. We conclude that CK1A/BTRCP/MBD3/NuRD signaling modulates GSC activation and malignancy, and that targeting this signaling could suppress GSC proliferation and GBM recurrence.
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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.