ArticleActa neuropathologica communications2021
Altered lipid metabolism marks glioblastoma stem and non-stem cells in separate tumor niches.
Article in Acta neuropathologica communications, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 86 papers.
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Who cites it
86 citing papers in PubMed.
- FXYD5 promotes the growth of glioblastoma by targeting the PI3K/AKT/ACSL4 signaling axis.Oncology reports · 2026Article
- Matrix stress relaxation drives glioblastoma cell response in viscoelastic biomaterials.Science advances · 2026Article
- Modeling gliomas with organoids: Classification, fidelity, and guidelines for translational neuro-oncology.Neuro-oncology · 2026Review
- FABP7: A Regulator of Neuro-Immune Metabolic Networks and Therapeutic Vulnerabilities in Glioma.Cancers · 2026Review
- BRI3 Orchestrates Lipid Metabolism and Autophagy in Glioblastoma: Implications for Tumor Cell Resilience.Biochemical genetics · 2026Article
- Advances in Brain Tumor Biomarkers: From Molecular Profiling to Liquid Biopsy and AI-Driven Detection.Cancers · 2026Review
- Organoids to Model Tumor Microenvironment in Progression of Pathogenesis and Treatment Resistance in Glioblastoma Multiforme.Brain sciences · 2026Review
- ARNT2 repression disrupts neuronal identity and promotes glioblastoma growth.Cell communication and signaling : CCS · 2026Article
- SCD1 and SCD5 modulate PARP-dependent DNA repair via fatty acid desaturation in glioblastoma.Cell reports · 2026Article
- Low-dose TNF-α drives malignant progression and lipid metabolism in glioblastoma through the TRAF2-FASN axis.Cell death discovery · 2026Article
- Loss of ABCA3 disrupts lipid balance and leads to AMPK-dependent suppression of SREBP1 in glioblastoma stem cells.Oncogene · 2026Article
- Accumulation of Siglec10European journal of immunology · 2026Article
- Elucidating the causal relationships between cerebrospinal fluid metabolites and glioblastoma insights from mendelian randomization study.Neurosurgical review · 2026Article
- Enhanced lipid metabolism serves as a metabolic vulnerability to polyunsaturated fatty acids in glioblastoma.JCI insight · 2026Article
- Stimulated Raman Scattering Imaging Enabled Biomarker Discovery for Precision Medicine.Chemical & biomedical imaging · 2025Review
- Tau impedes glioma progression by enhancing fatty acid β-oxidation-induced cellular senescence.Zoological research · 2025Article
- Biomarker Identification via Spatial Transcriptomics Profiling of Colorectal Cancer and Colorectal Cancer with Liver Metastasis Stem Cells.International journal of molecular sciences · 2025Article
- Spatial transcriptomics of glioblastoma defines biologically and clinically significant reprogramming patterns across unique spatial microenvironments.bioRxiv : the preprint server for biology · 2025Article
- Glioblastoma-enriched glycosphingolipids modulate the function of human iNKT cells.Neuro-oncology · 2025Article
- Lipid metabolism in cancer stem cells: reprogramming, mechanisms, crosstalk, and therapeutic approaches.Cellular oncology (Dordrecht, Netherlands) · 2025Review
26 more citing papers are in PubMed but not listed here.
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Authors and funding
13 authors.
Funding
Abstract
Glioblastoma (GBM) displays marked cellular and metabolic heterogeneity that varies among cellular microenvironments within a tumor. Metabolic targeting has long been advocated as a therapy against many tumors including GBM, but how lipid metabolism is altered to suit different microenvironmental conditions and whether cancer stem cells (CSCs) have altered lipid metabolism are outstanding questions in the field. We interrogated gene expression in separate microenvironments of GBM organoid models that mimic the transition between nutrient-rich and nutrient-poor pseudopalisading/perinecrotic tumor zones using spatial-capture RNA-sequencing. We revealed a striking difference in lipid processing gene expression and total lipid content between diverse cell populations from the same patient, with lipid enrichment in hypoxic organoid cores and also in perinecrotic and pseudopalisading regions of primary patient tumors. This was accompanied by regionally restricted upregulation of hypoxia-inducible lipid droplet-associated (HILPDA) gene expression in organoid cores and pseudopalisading regions of clinical GBM specimens, but not lower-grade brain tumors. CSCs have low lipid droplet accumulation compared to non-CSCs in organoid models and xenograft tumors, and prospectively sorted lipid-low GBM cells are functionally enriched for stem cell activity. Targeted lipidomic analysis of multiple patient-derived models revealed a significant shift in lipid metabolism between GBM CSCs and non-CSCs, suggesting that lipid levels may not be simply a product of the microenvironment but also may be a reflection of cellular state. CSCs had decreased levels of major classes of neutral lipids compared to non-CSCs, but had significantly increased polyunsaturated fatty acid production due to high fatty acid desaturase (FADS1/2) expression which was essential to maintain CSC viability and self-renewal. Our data demonstrate spatially and hierarchically distinct lipid metabolism phenotypes occur clinically in the majority of patients, can be recapitulated in laboratory models, and may represent therapeutic targets for GBM.
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