ArticleCell death & disease2022
Liver glycogen phosphorylase is upregulated in glioblastoma and provides a metabolic vulnerability to high dose radiation.
Article in Cell death & disease, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed, 22 citations in OpenAlex.
- Development and characterization of triazole-based WDR5 inhibitors for the treatment of glioblastoma.JCI insight · 2026Article
- Chicoric acid targets PYGL to normalize glycogenolysis-driven glycolysis to suppress non-small cell lung cancer.Cellular & molecular biology letters · 2026Article
- Extracellular ATP promotes endocrine resistance in ER+ breast cancer through upregulation of PYGL.Cell death & disease · 2026Article
- TMAO Supplementation to High-Carbohydrate Diet Reprogrammed Hepatic Metabolism and Intestinal Microbiota to Improve Liver Health and Disease Resistance ofMicroorganisms · 2026Article
- Crosstalk between acetylation modification and autophagy in cancer: roles, mechanisms, and therapeutic potential.Cell death discovery · 2025Review
- Article
- Early Detection of Glioma: Investigating Inflammatory Markers (CRP), Kidney, and Liver Function.CNS & neurological disorders drug targets · 2025Article
- Uncovering the molecular targets of phytocannabinoids: mechanistic insights from inverse molecular docking fingerprint approaches.Frontiers in pharmacology · 2025Article
- A systems biology approach to unveil shared therapeutic targets and pathological pathways across major human cancers.Computational and structural biotechnology journal · 2025Article
- Article
- Evidence for the Quercetin Binding Site of Glycogen Phosphorylase as a Target for Liver-Isoform-Selective Inhibitors against Glioblastoma: Investigation of Flavanols Epigallocatechin Gallate and Epigallocatechin.Journal of agricultural and food chemistry · 2024Article
- The link between amyloid β and ferroptosis pathway in Alzheimer's disease progression.Cell death & disease · 2024Article
- Synthesis, In Silico and Kinetics Evaluation ofInternational journal of molecular sciences · 2024Article
- Inhibition of mitochondrial fission activates glycogen synthesis to support cell survival in colon cancer.Cell death & disease · 2023Article
- miR-22-enriched breast cancer cells display repressed glycolytic metabolism, increased glycogen synthesis, and reduced survival in low glucose conditions.Molecular biology reports · 2023Article
- Design and Synthesis of 3-(β-d-Glucopyranosyl)-4-amino/4-guanidino Pyrazole Derivatives and Analysis of Their Glycogen Phosphorylase Inhibitory Potential.Molecules (Basel, Switzerland) · 2023Article
- Machine learning-based identification of glycosyltransferase-related mRNAs for improving outcomes and the anti-tumor therapeutic response of gliomas.Frontiers in pharmacology · 2023Article
- Autophagy-dependent ferroptosis as a potential treatment for glioblastoma.Frontiers in oncology · 2023Review
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Authors and funding
17 authors at 9 institutions in 4 countries.
Funding
Abstract
Channelling of glucose via glycogen, known as the glycogen shunt, may play an important role in the metabolism of brain tumours, especially in hypoxic conditions. We aimed to dissect the role of glycogen degradation in glioblastoma (GBM) response to ionising radiation (IR). Knockdown of the glycogen phosphorylase liver isoform (PYGL), but not the brain isoform (PYGB), decreased clonogenic growth and survival of GBM cell lines and sensitised them to IR doses of 10-12 Gy. Two to five days after IR exposure of PYGL knockdown GBM cells, mitotic catastrophy and a giant multinucleated cell morphology with senescence-like phenotype developed. The basal levels of the lysosomal enzyme alpha-acid glucosidase (GAA), essential for autolysosomal glycogen degradation, and the lipidated forms of gamma-aminobutyric acid receptor-associated protein-like (GABARAPL1 and GABARAPL2) increased in shPYGL U87MG cells, suggesting a compensatory mechanism of glycogen degradation. In response to IR, dysregulation of autophagy was shown by accumulation of the p62 and the lipidated form of GABARAPL1 and GABARAPL2 in shPYGL U87MG cells. IR increased the mitochondrial mass and the colocalisation of mitochondria with lysosomes in shPYGL cells, thereby indicating reduced mitophagy. These changes coincided with increased phosphorylation of AMP-activated protein kinase and acetyl-CoA carboxylase 2, slower ATP generation in response to glucose loading and progressive loss of oxidative phosphorylation. The resulting metabolic deficiencies affected the availability of ATP required for mitosis, resulting in the mitotic catastrophy observed in shPYGL cells following IR. PYGL mRNA and protein levels were higher in human GBM than in normal human brain tissues and high PYGL mRNA expression in GBM correlated with poor patient survival. In conclusion, we show a major new role for glycogen metabolism in GBM cancer. Inhibition of glycogen degradation sensitises GBM cells to high-dose IR indicating that PYGL is a potential novel target for the treatment of GBMs.
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