ArticleEMBO molecular medicine2020
Therapeutic implications of altered cholesterol homeostasis mediated by loss of CYP46A1 in human glioblastoma.
Article in EMBO molecular medicine, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 53 papers.
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Who cites it
53 citing papers in PubMed, 78 citations in OpenAlex.
- CYP46A1-Targeted Treatment Alleviates Long-Term White Matter Injury Following Traumatic Brain Injury by Promoting Cholesterol Metabolic Clearance and Remyelination.CNS neuroscience & therapeutics · 2026Article
- CYP46A1 activation by low-dose efavirenz uncovers the link between brain cholesterol metabolism, energetics, and vasculature.Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie · 2026Article
- Multiscale analysis and optimal glioma therapeutic candidate discovery using the CANDO platform.Journal of cheminformatics · 2026Article
- Cancer Cell-Intrinsic Cholesterol Induces Lipid-Associated Macrophage Differentiation via SP1 Palmitoylation to Promote Prostate Cancer Progression.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Adaptaquin is selectively toxic to glioma stem cells through disruption of iron and cholesterol metabolism.Molecular oncology · 2026Article
- Lipid metabolic plasticity in glioblastoma: mechanisms, tumor microenvironment remodeling, and therapeutic opportunities.Frontiers in oncology · 2026Review
- Histone methyltransferase PRDM9 promotes survival of drug-tolerant persister cells in glioblastoma.Nature communications · 2025Article
- Cut the fat: targeting cholesterol and lipid metabolism in glioblastoma.Cell death & disease · 2025Review
- Frequency-Dependent Mechanism of 24-Hydroxycholesterol-Mediated Modulation of Neurotransmitter Release at the Mouse Neuromuscular Junction: The Role of Reactive Oxygen Species.Neurochemical research · 2025Article
- Dysregulation of cholesterol homeostasis in cancer pathogenesis.Cellular and molecular life sciences : CMLS · 2025Review
- Serum Mac2-binding protein glycosylated isomer (M2BPGi) as a prognostic biomarker in pancreatic ductal adenocarcinoma: iCAFs-derived M2BPGi drives tumor invasion.Journal of gastroenterology · 2025Article
- Brain Cytochrome P450: Navigating Neurological Health and Metabolic Regulation.Journal of xenobiotics · 2025Review
- The Cross-Talk Between the Peripheral and Brain Cholesterol Metabolisms.Current issues in molecular biology · 2025Review
- Drug repurposing screen targeting PARP identifies cytotoxic activity of efavirenz in high-grade serous ovarian cancer.Molecular therapy. Oncology · 2024Article
- A novel model based on lipid metabolism-related genes associated with immune microenvironment predicts metastasis of breast cancer.Discover oncology · 2024Article
- Discovery and Optimization of N-Arylated Tetracyclic Dicarboximides That Target Primary Glioma Stem-like Cells.Journal of medicinal chemistry · 2024Article
- Bile acid signaling in the regulation of whole body metabolic and immunological homeostasis.Science China. Life sciences · 2024Review
- 7,8-Dihydroxy Efavirenz Is Not as Effective in CYP46A1 Activation In Vivo as Efavirenz or Its 8,14-Dihydroxy Metabolite.International journal of molecular sciences · 2024Article
- Therapeutic Applications of Oxysterols and Derivatives in Age-Related Diseases, Infectious and Inflammatory Diseases, and Cancers.Advances in experimental medicine and biology · 2024Review
- Oxysterols as Biomarkers of Aging and Disease.Advances in experimental medicine and biology · 2024Article
Corrections and comments
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Authors and funding
15 authors at 6 institutions in 4 countries.
Funding
Abstract
Dysregulated cholesterol metabolism is a hallmark of many cancers, including glioblastoma (GBM), but its role in disease progression is not well understood. Here, we identified cholesterol 24-hydroxylase (CYP46A1), a brain-specific enzyme responsible for the elimination of cholesterol through the conversion of cholesterol into 24(S)-hydroxycholesterol (24OHC), as one of the most dramatically dysregulated cholesterol metabolism genes in GBM. CYP46A1 was significantly decreased in GBM samples compared with normal brain tissue. A reduction in CYP46A1 expression was associated with increasing tumour grade and poor prognosis in human gliomas. Ectopic expression of CYP46A1 suppressed cell proliferation and in vivo tumour growth by increasing 24OHC levels. RNA-seq revealed that treatment of GBM cells with 24OHC suppressed tumour growth through regulation of LXR and SREBP signalling. Efavirenz, an activator of CYP46A1 that is known to penetrate the blood-brain barrier, inhibited GBM growth in vivo. Our findings demonstrate that CYP46A1 is a critical regulator of cellular cholesterol in GBM and that the CYP46A1/24OHC axis is a potential therapeutic target.
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