ArticleNeuro-oncology2023
Sterol regulatory element-binding protein 2 maintains glioblastoma stem cells by keeping the balance between cholesterol biosynthesis and uptake.
Article in Neuro-oncology, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.
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Who cites it
28 citing papers in PubMed, 31 citations in OpenAlex.
- Low-Density Lipoprotein Receptor-Targeted Biomimetic Nanoplatform Suppresses Glioblastoma Stemness and Remodels Antitumor Immunity via Dual Metabolic Disruption.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Thr3/Ser90 phosphorylation-stabilized S100A8 regulates cholesterol metabolism in glioblastoma stem cells.Oncogene · 2026Article
- Subtype-specific associations between serum lipid profiles and disease severity in patients with amyotrophic lateral sclerosis.Biomedical reports · 2026Article
- Status and trends in glioblastoma lipid metabolism research: a bibliometric analysis.Discover oncology · 2026Review
- Simvastatin reprograms lipid metabolism in B16.F10 melanoma cells to favor an early resistant phenotype.Scientific reports · 2026Article
- Understanding Glioblastoma Dynamics Using 3D Organoids and Engineered Extracellular Matrix.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Metabolic dependencies and neural progenitor dysregulation: driving forces in paediatric high-grade glioma development.Cancer metastasis reviews · 2026Review
- The Natural Triterpenoid Alisol B Overcomes Temozolomide Resistance in Glioblastoma Through Multi-Target Mechanisms: Coordinated Epigenetic, Metabolic, and Cell-Cycle Reprogramming.International journal of molecular sciences · 2026Article
- Cancer-associated adipocytes confer CDK4/6 inhibitor resistance in ER+ breast cancer through an IL-6/STAT3/SREBF2 axis coupled with cholesterol metabolism and cell cycle reprogramming.International journal of biological sciences · 2026Article
- Activated astrocytes drive the accumulation of apolipoprotein E at the brain tumor edge.Brain tumor pathology · 2026Article
- RORα: a critical nexus in the crosstalk between cholesterol metabolism and macrophage polarization.Frontiers in immunology · 2026Review
- Hippo pathway effectors are associated with glioma patient survival, control cell proliferation and sterol metabolism through TEAD3.Brain pathology (Zurich, Switzerland) · 2025Article
- Nuclear cholesterol regulates nuclear size and DNA damage responses in cancer stem cells.Neuro-oncology · 2025Article
- Understanding proneural-mesenchymal transition using patient-derived glioma stem-like cell (GSC) organoids and engineered extracellular matrix.bioRxiv : the preprint server for biology · 2025Article
- Mitochondrial metabolism and cancer therapeutic innovation.Signal transduction and targeted therapy · 2025Review
- Integrative analysis of cholesterol homeostasis reveals prognostic subtypes and immune features in clear cell renal cell carcinoma.Discover oncology · 2025Article
- Gene2role: a role-based gene embedding method for comparative analysis of signed gene regulatory networks.BMC bioinformatics · 2025Article
- Inhibition of MBTPS1 enhances antitumor immunity and potentiates anti-PD-1 immunotherapy.Nature communications · 2025Article
- The Role of Cholesterol Metabolism and Its Regulation in Tumor Development.Cancer medicine · 2025Review
- PIN1 Prolyl Isomerase Promotes Initiation and Progression of Bladder Cancer through the SREBP2-Mediated Cholesterol Biosynthesis Pathway.Cancer discovery · 2025Article
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Authors and funding
30 authors at 13 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundGlioblastomas (GBMs) display striking dysregulation of metabolism to promote tumor growth. Glioblastoma stem cells (GSCs) adapt to regions of heterogeneous nutrient availability, yet display dependency on de novo cholesterol biosynthesis. The transcription factor Sterol Regulatory Element-Binding Protein 2 (SREBP2) regulates cholesterol biosynthesis enzymes and uptake receptors. Here, we investigate adaptive behavior of GSCs under different cholesterol supplies.
methodsIn silico analysis of patient tumors demonstrated enrichment of cholesterol synthesis associated with decreased angiogenesis. Comparative gene expression of cholesterol biosynthesis enzymes in paired GBM specimens and GSCs were performed. In vitro and in vivo loss-of-function genetic and pharmacologic assays were conducted to evaluate the effect of SREBP2 on GBM cholesterol biosynthesis, proliferation, and self-renewal. Chromatin immunoprecipitation quantitative real-time PCR was leveraged to map the regulation of SREBP2 to cholesterol biosynthesis enzymes and uptake receptors in GSCs.
resultsCholesterol biosynthetic enzymes were expressed at higher levels in GBM tumor cores than in invasive margins. SREBP2 promoted cholesterol biosynthesis in GSCs, especially under starvation, as well as proliferation, self-renewal, and tumor growth. SREBP2 governed the balance between cholesterol biosynthesis and uptake in different nutrient conditions.
conclusionsSREBP2 displays context-specific regulation of cholesterol biology based on its availability in the microenvironment with induction of cholesterol biosynthesis in the tumor core and uptake in the margin, informing a novel treatment strategy for GBM.
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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.