ArticleThe Journal of clinical investigation2023
Superenhancer activation of KLHDC8A drives glioma ciliation and hedgehog signaling.
Article in The Journal of clinical investigation, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
What it found
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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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
18 citing papers in PubMed, 35 citations in OpenAlex.
- Global RNA expression analysis of patient samples identified potential diagnostic biomarkers specific for peritoneal, ovarian and deep endometriosis.Scientific reports · 2026Article
- The TRiC/CCT Complex at the Crossroads of Metabolism and Hypoxia in GBM: Implications for IDH-Dependent Therapeutic Targeting.International journal of molecular sciences · 2025Review
- Inhibition of PI3K and Hedgehog Signaling Pathway Inhibits Hypoxia-Induced Vasculogenic Mimicry Formation in Ovarian Cancer Stem Cells.Balkan medical journal · 2025Article
- Transcriptomic Profiling of Zebrafish Mutant forInternational journal of molecular sciences · 2025Article
- Epigenetic Alterations in Glioblastoma Multiforme as Novel Therapeutic Targets: A Scoping Review.International journal of molecular sciences · 2025Article
- Primary cilia and cancer: a tale of many faces.Oncogene · 2025Review
- Characteristics of the Kelch domain containing (KLHDC) subfamily and relationships with diseases.FEBS letters · 2025Review
- NAdvanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Comprehensive review of drug resistance in mammalian cancer stem cells: implications for cancer therapy.Cancer cell international · 2024Review
- Tumor immune microenvironment of colorectal cancer identifies novel prognostic signature and potential therapeutic drugs.Cancer biomarkers : section A of Disease markers · 2024Article
- Evaluating KLHDC8A as a biomarker for glioma: impact on survival and proliferation through the Wnt/β-catenin pathway.Discover oncology · 2024Article
- The Role of HDAC6 in Glioblastoma Multiforme: A New Avenue to Therapeutic Interventions?Biomedicines · 2024Review
- Cancer stem cells: advances in knowledge and implications for cancer therapy.Signal transduction and targeted therapy · 2024Review
- Primary cilia-associated signalling in squamous cell carcinoma of head and neck region.Frontiers in oncology · 2024Review
- Article
- Cilia at the Crossroads of Tumor Treating Fields and Chemotherapy.Developmental neuroscience · 2023Review
- Mouse models of nonalcoholic steatohepatitis and their application to new drug development.Archives of pharmacal research · 2022Review
- Breaking down glioma primary cilia disassembly.Neuro-oncology advancesReview
Corrections and comments
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Authors and funding
12 authors at 5 institutions in 3 countries.
Funding
Abstract
Glioblastoma ranks among the most aggressive and lethal of all human cancers. Self-renewing, highly tumorigenic glioblastoma stem cells (GSCs) contribute to therapeutic resistance and maintain cellular heterogeneity. Here, we interrogated superenhancer landscapes of primary glioblastoma specimens and patient-derived GSCs, revealing a kelch domain-containing gene, specifically Kelch domain containing 8A (KLHDC8A) with a previously unknown function as an epigenetically driven oncogene. Targeting KLHDC8A decreased GSC proliferation and self-renewal, induced apoptosis, and impaired in vivo tumor growth. Transcription factor control circuitry analyses revealed that the master transcriptional regulator SOX2 stimulated KLHDC8A expression. Mechanistically, KLHDC8A bound chaperonin-containing TCP1 (CCT) to promote the assembly of primary cilia to activate hedgehog signaling. KLHDC8A expression correlated with Aurora B/C Kinase inhibitor activity, which induced primary cilia and hedgehog signaling. Combinatorial targeting of Aurora B/C kinase and hedgehog displayed augmented benefit against GSC proliferation. Collectively, superenhancer-based discovery revealed KLHDC8A as what we believe to be a novel molecular target of cancer stem cells that promotes ciliogenesis to activate the hedgehog pathway, offering insights into therapeutic vulnerabilities for glioblastoma treatment.
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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.