ArticleCell death & disease2013
Epigenetic status of argininosuccinate synthetase and argininosuccinate lyase modulates autophagy and cell death in glioblastoma.
Article in Cell death & disease, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 100 papers.
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Who cites it
100 citing papers in PubMed, 165 citations in OpenAlex.
- Arginine deprivation induces prolonged autophagy activation and ROS-dependent cell death in glioblastoma multiforme.CNS oncology · 2026Article
- Arginine Deprivation of ASS1-Deficient Cancers Drives Mistranslation and Shared Neoepitope Production.Cancer research · 2026Article
- Integrative bulk and single-cell analyses implicate ASL in MIF-associated myeloid programs in glioblastoma.Functional & integrative genomics · 2026Article
- Context-dependent synthetic lethality - an emerging precision therapeutic approach.Nature reviews. Cancer · 2026Review
- The nutrigenomic-epigenetic axis in cancer: from dietary bioactives to precision oncology.Nutrition & metabolism · 2026Review
- Arginine deprivation induces ROS dependent autophagic cell death in human acute myeloid leukemia cells.Human cell · 2026Article
- Exploiting nanopore sequencing advances for tRNA sequencing of human cancer models.NAR cancer · 2025Article
- Screening of targets related to amino acid metabolism in glioma to identify the tumor-promoting effects of its core gene ASL.Scientific reports · 2025Article
- ASS1 inhibits liver cancer by promoting CAD ubiquitination and reversing the urea cycle and pyrimidine synthesis imbalance.Hepatology communications · 2025Article
- The therapeutic potential of pegylated arginase I treatment in glioblastoma.Scientific reports · 2025Article
- Invasive lobular carcinoma: integrated multi-omics analysis reveals silencing of Argininosuccinate synthase and upregulation of nucleotide biosynthesis in tamoxifen resistance.Cell death & disease · 2025Article
- BCL-XL Protects ASS1-Deficient Cancers from Arginine Starvation-Induced Apoptosis.Clinical cancer research : an official journal of the American Association for Cancer Research · 2025Article
- Amino acid metabolism in glioblastoma pathogenesis, immune evasion, and treatment resistance.Cancer cell international · 2025Review
- Vitamin B6 Pathway Maintains Glioblastoma Cell Survival in 3D Spheroid Cultures.International journal of molecular sciences · 2024Article
- Microglia and macrophage metabolism: a regulator of cerebral gliomas.Cell & bioscience · 2024Review
- From the Inside Out: Exposing the Roles of Urea Cycle Enzymes in Tumors and Their Micro and Macro Environments.Cold Spring Harbor perspectives in medicine · 2024Review
- The strain-dependent cytostatic activity of Lactococcus lactis on CRC cell lines is mediated through the release of arginine deiminase.Microbial cell factories · 2024Article
- The nonessential amino acid cysteine is required to prevent ferroptosis in acute myeloid leukemia.Blood advances · 2024Article
- Therapeutic potential of arginine deprivation therapy for gliomas: a systematic review of the existing literature.Frontiers in pharmacology · 2024Review
- Unlocking the Potential of Arginine Deprivation Therapy: Recent Breakthroughs and Promising Future for Cancer Treatment.International journal of molecular sciences · 2023Review
40 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
14 authors at 7 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Arginine deprivation, either by nutritional starvation or exposure to ADI-PEG20, induces adaptive transcriptional upregulation of ASS1 and ASL in glioblastoma multiforme ex vivo cultures and cell lines. This adaptive transcriptional upregulation is blocked by neoplasia-specific CpG island methylation in either gene, causing arginine auxotrophy and cell death. In cells with methylated ASS1 or ASL CpG islands, ADI-PEG20 initially induces a protective autophagic response, but abrogation of this by chloroquine accelerates and potentiates cytotoxicity. Concomitant methylation in the CpG islands of both ASS1 and ASL, observed in a subset of cases, confers hypersensitivity to ADI-PEG20. Cancer stem cells positive for CD133 and methylation in the ASL CpG island retain sensitivity to ADI-PEG20. Our results show for the first time that epigenetic changes occur in both of the two key genes of arginine biosynthesis in human cancer and confer sensitivity to therapeutic arginine deprivation. We demonstrate that methylation status of the CpG islands, rather than expression levels per se of the genes, predicts sensitivity to arginine deprivation. Our results suggest a novel therapeutic strategy for this invariably fatal central nervous system neoplasm for which we have identified robust biomarkers and which overcomes the limitations to conventional chemotherapy imposed by the blood/brain barrier.
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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.