ArticleNature communications2023
Hypoxanthine phosphoribosyl transferase 1 metabolizes temozolomide to activate AMPK for driving chemoresistance of glioblastomas.
Article in Nature communications, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
What it found
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Who cites it
26 citing papers in PubMed, 40 citations in OpenAlex.
- Mitophagy-Competent Cancer-Associated Fibroblasts Fuel Chemoresistance by Rewiring Pyrimidine Metabolism in Pancreatic Cancer.Cancer research · 2026Article
- Exosome Secretion Drives Chemo-Resistance of Temozolomide in Glioblastoma.Journal of extracellular biology · 2026Article
- ARL13B is regulated by the ERK/P90 pathway and mediates TMZ resistance in glioblastoma via microvesicles.Scientific reports · 2026Article
- Exosomal circ_0050688 Shapes a Chemoresistant Microenvironment by Driving Spatial Resistance Spreading in Glioblastoma via the MDM2 Pathway.Biomolecules · 2026Article
- Chemotherapy induces multiple sclerosis-like neuropathologies that can be rescued by clobetasol.Cell death and differentiation · 2026Article
- Discovery of vasodilatory effects of NaActa pharmacologica Sinica · 2026Article
- The structural requirements of 3,5-substituted oxindoles that determine selective AMPK or GSK3β inhibition.RSC medicinal chemistry · 2026Article
- AMPK at the interface of nutrient sensing, metabolic flux and energy homeostasis.Nature metabolism · 2026Review
- Local therapeutic platform prevents postsurgical GBM recurrence by diminishing GICs and reshaping immunosuppressive microenvironment.Nature communications · 2025Article
- Tumor-derived apolipoprotein E confers resistance to temozolomide in pancreatic neuroendocrine tumors.Cell death & disease · 2025Article
- Temozolomide-Derived AIC Is Incorporated into Purine Synthesis in Glioblastoma.Chemical research in toxicology · 2025Article
- Hypoxanthine Promotes Pulmonary Vascular Remodeling and Adenosine Deaminase Is a Therapeutic Target for Pulmonary Hypertension.JACC. Basic to translational science · 2025Article
- Purine nucleoside phosphorylase dominates Influenza A virus replication and host hyperinflammation through purine salvage.Signal transduction and targeted therapy · 2025Article
- Post-translational modifications in DNA damage repair: mechanisms underlying temozolomide resistance in glioblastoma.Oncogene · 2025Review
- Glioblastoma multiforme: an updated overview of temozolomide resistance mechanisms and strategies to overcome resistance.Discover oncology · 2025Review
- Exosomes in the Chemoresistance of Glioma: Key Point in Chemoresistance.Journal of cellular and molecular medicine · 2025Review
- Calnexin promotes glioblastoma progression by inducing protective mitophagy through the MEK/ERK/BNIP3 pathway.Theranostics · 2025Article
- Towards Effective Treatment of Glioblastoma: The Role of Combination Therapies and the Potential of Phytotherapy and Micotherapy.Current issues in molecular biology · 2024Review
- AMPK: The energy sensor at the crossroads of aging and cancer.Seminars in cancer biology · 2024Review
- Article
Corrections and comments
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Authors and funding
20 authors at 7 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Temozolomide (TMZ) is a standard treatment for glioblastoma (GBM) patients. However, TMZ has moderate therapeutic effects due to chemoresistance of GBM cells through less clarified mechanisms. Here, we demonstrate that TMZ-derived 5-aminoimidazole-4-carboxamide (AICA) is converted to AICA ribosyl-5-phosphate (AICAR) in GBM cells. This conversion is catalyzed by hypoxanthine phosphoribosyl transferase 1 (HPRT1), which is highly expressed in human GBMs. As the bona fide activator of AMP-activated protein kinase (AMPK), TMZ-derived AICAR activates AMPK to phosphorylate threonine 52 (T52) of RRM1, the catalytic subunit of ribonucleotide reductase (RNR), leading to RNR activation and increased production of dNTPs to fuel the repairment of TMZ-induced-DNA damage. RRM1 T52A expression, genetic interruption of HPRT1-mediated AICAR production, or administration of 6-mercaptopurine (6-MP), a clinically approved inhibitor of HPRT1, blocks TMZ-induced AMPK activation and sensitizes brain tumor cells to TMZ treatment in mice. In addition, HPRT1 expression levels are positively correlated with poor prognosis in GBM patients who received TMZ treatment. These results uncover a critical bifunctional role of TMZ in GBM treatment that leads to chemoresistance. Our findings underscore the potential of combined administration of clinically available 6-MP to overcome TMZ chemoresistance and improve GBM treatment.
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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 Socratic graph.