ArticleCell death and differentiation2012
Hypoxia-induced mixed-lineage leukemia 1 regulates glioma stem cell tumorigenic potential.
Article in Cell death and differentiation, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 79 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
79 citing papers in PubMed, 139 citations in OpenAlex.
- Spatial heterogeneity of malignant molecular markers in glioma revealed by stereotactic biopsy.Discover oncology · 2026Article
- Silencing KMT2A with siRNA induces apoptosis and cell cycle arrest in high-grade serous ovarian carcinoma cells by modulating GOF p53-dependent pathways, highlighting its potential as a therapeutic target.Medical oncology (Northwood, London, England) · 2025Article
- Epigenetic regulation of histone modifications in glioblastoma: recent advances and therapeutic insights.Biomarker research · 2025Review
- A clinically relevant model and method to study necrosis as a driving force in glioma restructuring and progression.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Hyperbaric oxygen promotes both the proliferation and chemosensitization of glioblastoma cells by inhibiting HIF1α/HIF2α-ABCG2.Frontiers in molecular neuroscience · 2025Article
- HIF-1α signaling: Essential roles in tumorigenesis and implications in targeted therapies.Genes & diseases · 2024Review
- MLL1 inhibits the neurogenic potential of SCAPs by interacting with WDR5 and repressing HES1.International journal of oral science · 2023Article
- macroH2A2 antagonizes epigenetic programs of stemness in glioblastoma.Nature communications · 2023Article
- Homeobox A3 and KDM6A cooperate in transcriptional control of aerobic glycolysis and glioblastoma progression.Neuro-oncology · 2023Article
- WDR5 represents a therapeutically exploitable target for cancer stem cells in glioblastoma.Genes & development · 2023Article
- ABTC-0904: targeting glioma stem cells in GBM: a phase 0/II study of hedgehog pathway inhibitor GDC-0449.Journal of neuro-oncology · 2023Article
- The function of histone methylation and acetylation regulators in GBM pathophysiology.Frontiers in oncology · 2023Review
- Roles of Chromatin Remodelling and Molecular Heterogeneity in Therapy Resistance in Glioblastoma.Cancers · 2022Review
- Review
- Gene regulation by histone-modifying enzymes under hypoxic conditions: a focus on histone methylation and acetylation.Experimental & molecular medicine · 2022Review
- Crosstalk of Epigenetic and Metabolic Signaling Underpinning Glioblastoma Pathogenesis.Cancers · 2022Review
- The metabolomic landscape plays a critical role in glioma oncogenesis.Cancer science · 2022Review
- Necrotic reshaping of the glioma microenvironment drives disease progression.Acta neuropathologica · 2022Review
- Heterogeneity of glioblastoma stem cells in the context of the immune microenvironment and geospatial organization.Frontiers in oncology · 2022Review
- Exploring glioblastoma stem cell heterogeneity: Immune microenvironment modulation and therapeutic opportunities.Frontiers in oncology · 2022Review
19 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
9 authors at 3 institutions in 1 country.
Funding
Abstract
Normal stem cells reside in functional niches critical for self-renewal and maintenance. Neural and hematopoietic stem cell niches, in particular, are characterized by restricted availability of oxygen and the resulting regulation by hypoxia-inducible factors (HIFs). Glioblastoma multiforme (GBM) is the most common malignant brain tumor and also contains high degrees of hypoxia. Heterogeneity within the neoplastic compartment has been well characterized in GBM and may be derived from genetic and epigenetic sources that co-evolve during malignant progression. Recent experimental evidence has supported the importance of hypoxia in glioma stem cell (GSC) niches. We hypothesized that HIFs require epigenetic-modifying proteins to promote tumor malignancy in GBM. Here we demonstrate that in GBM the histone methyltransferase mixed-lineage leukemia 1 (MLL1) is induced by hypoxia and enhances hypoxic responses. Loss of MLL1 reduces the expression of HIF transcripts and HIF2α protein. Targeting MLL1 by RNA interference inhibited the expression of HIF2α and target genes, including vascular endothelial growth factor (VEGF). GSCs expressed higher levels of MLL1 than matched non-stem tumor cells and depletion of MLL1 reduced GSC self-renewal, growth, and tumorigenicity. These studies have uncovered a novel mechanism mediating tumor hypoxic responses linking microenvironmental regulation of epigenetic-modifying proteins to cellular heterogeneity and provide rationale for the design of more sophisticated clinical approaches targeting epigenetic regulation.
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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.