ArticleThe Journal of clinical investigation2023
Human endogenous retrovirus K contributes to a stem cell niche in glioblastoma.
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 30 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.
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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
30 citing papers in PubMed, 47 citations in OpenAlex.
- Expression of Human Endogenous Retroviruses in Peripheral Blood of Acute and Chronically HIV-Infected Subjects and Effect of Antiretroviral Therapy.International journal of molecular sciences · 2026Article
- Immune landscape of the affected brain in Rasmussen encephalitis.Scientific reports · 2026Article
- HERV-K TM Subunit Elicits CD8Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Human Endogenous Retroviruses and Diseases.MedComm · 2025Review
- Strict retroelement regulation is frequently lost following cancer transformation and generates a promising reservoir of cancer biomarkers.Mobile DNA · 2025Article
- Immunologic specificity in glioblastoma: Antigen discovery and translational implications.Neuro-oncology advances · 2025Review
- Elucidating the association between TLR-4 expression and the clinical course of glioblastoma leptomeningeal disease.British journal of cancer · 2025Article
- HERV-derived epitopes represent new targets for T-cell-based immunotherapies in ovarian cancer.Journal for immunotherapy of cancer · 2025Article
- Article
- The Role of Human Endogenous Retroviruses in the Initiation and Progression of Melanoma.Biomedicines · 2025Review
- The Role of Viruses in the Glioma Tumor Microenvironment: Immunosuppressors or Primers for Anti-Tumor Immunity?Cancers · 2025Review
- Human endogenous retroviruses (HERVs) associated with glioblastoma risk and prognosis.Cancer gene therapy · 2025Article
- Glioblastoma Stem Cells at the Nexus of Tumor Heterogeneity, Immune Evasion, and Therapeutic Resistance.Cells · 2025Review
- Retrotransposon: an insight into neurological disorders from perspectives of neurodevelopment and aging.Translational neurodegeneration · 2025Review
- Activating antiviral immune responses potentiates immune checkpoint inhibition in glioblastoma models.The Journal of clinical investigation · 2025Article
- Exploring viral mimicry combined with epigenetics and tumor immunity: new perspectives in cancer therapy.International journal of biological sciences · 2025Review
- Article
- The glioblastoma virome across tumor and extracellular compartments.Frontiers in oncology · 2025Article
- Exploring viral mimicry combined with epigenetics and tumor immunity: new perspectives in cancer therapy.International journal of biological sciences · 2025Review
- Review
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Authors and funding
27 authors at 5 institutions in 1 country.
Funding
Abstract
Human endogenous retroviruses (HERVs) are ancestral viral relics that constitute nearly 8% of the human genome. Although normally silenced, the most recently integrated provirus HERV-K (HML-2) can be reactivated in certain cancers. Here, we report pathological expression of HML-2 in malignant gliomas in both cerebrospinal fluid and tumor tissue that was associated with a cancer stem cell phenotype and poor outcomes. Using single-cell RNA-Seq, we identified glioblastoma cellular populations with elevated HML-2 transcripts in neural progenitor-like cells (NPC-like) that drive cellular plasticity. Using CRISPR interference, we demonstrate that HML-2 critically maintained glioblastoma stemness and tumorigenesis in both glioblastoma neurospheres and intracranial orthotopic murine models. Additionally, we demonstrate that HML-2 critically regulated embryonic stem cell programs in NPC-derived astroglia and altered their 3D cellular morphology by activating the nuclear transcription factor OCT4, which binds to an HML-2-specific long-terminal repeat (LTR5Hs). Moreover, we discovered that some glioblastoma cells formed immature retroviral virions, and inhibiting HML-2 expression with antiretroviral drugs reduced reverse transcriptase activity in the extracellular compartment, tumor viability, and pluripotency. Our results suggest that HML-2 fundamentally contributes to the glioblastoma stem cell niche. Because persistence of glioblastoma stem cells is considered responsible for treatment resistance and recurrence, HML-2 may serve as a unique therapeutic target.
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What Socratic holds
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 Socratic graph.