ArticleOncogene2016
Gas6/Axl is the sensor of arginine-auxotrophic response in targeted chemotherapy with arginine-depleting agents.
Article in Oncogene, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed, 26 citations in OpenAlex.
- Etoposide-induced protein 2.4 homolog promotes argininosuccinate synthase 1 and cancer cell survival upon arginine deprivation.Cellular & molecular biology letters · 2025Article
- STAMBPL1/TRIM21 Balances AXL Stability Impacting Mesenchymal Phenotype and Immune Response in KIRC.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Reactive Oxygen Species Mechanisms that Regulate Protein-Protein Interactions in Cancer.International journal of molecular sciences · 2024Review
- The addition of arginine deiminase potentiates Mithramycin A-induced cell death in patient-derived glioblastoma cells via ATF4 and cytochrome C.Cancer cell international · 2023Article
- Enhancing the Effect of Tumor Necrosis Factor-Related Apoptosis-Inducing Ligand Signaling and Arginine Deprivation in Melanoma.International journal of molecular sciences · 2021Review
- Arginine Signaling and Cancer Metabolism.Cancers · 2021Review
- Targeting the Proline-Glutamine-Asparagine-Arginine Metabolic Axis in Amino Acid Starvation Cancer Therapy.Pharmaceuticals (Basel, Switzerland) · 2021Review
- Genome-wide CRISPR/Cas9 knockout screening uncovers a novel inflammatory pathway critical for resistance to arginine-deprivation therapy.Theranostics · 2021Article
- Targeting TAM to Tame Pancreatic Cancer.Targeted oncology · 2020Review
- Collaboration Between RSK-EphA2 and Gas6-Axl RTK Signaling in Arginine Starvation Response That Confers Resistance to EGFR Inhibitors.Translational oncology · 2020Article
- Anti-inflammation and anti-apoptosis effects of growth arrest-specific protein 6 in acute liver injury induced by LPS/D-GalN in mice.Acta cirurgica brasileira · 2020Article
- Cancer Stem Cells: Emergent Nature of Tumor Emergency.Frontiers in genetics · 2018Article
- Chromatin remodeling system p300-HDAC2-Sin3A is involved in Arginine Starvation-Induced HIF-1α Degradation at the ASS1 promoter for ASS1 Derepression.Scientific reports · 2017Article
- Article
Corrections and comments
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Authors and funding
11 authors at 4 institutions in 2 countries.
Funding
Abstract
Many human malignancies lack de novo biosynthesis of arginine (Arg) as the key enzyme argininosuccinate synthetase 1 (ASS1) is silenced. These tumors acquire ectopic Arg for survival, and depleting this source by Arg-depleting recombinant enzyme ADI-PEG20 results in cell death. Mechanisms underlying Arg auxotrophy in these tumors and how they respond to Arg-auxotrophic stress are poorly understood. Here, we report that an immediate-early event of Arg-auxotrophic response involves reactive oxygen species-mediated secretion of Gas6, which interacts with its receptor Axl and activates the downstream Ras/PI3K/Akt growth signal leading to accumulation of c-Myc by protein stabilization. Arg-auxotrophic challenge also transcriptionally upregulates c-Myc expression, which provides a feedback mechanism to enhance Axl expression. c-Myc is a positive regulator of ASS1, but elevated ASS1 provides a feedback mechanism to suppress c-Myc and Axl. Our results revealed multiple inter-regulatory pathways in Arg-auxotrophic response, consisting of Axl, c-Myc and ASS1, which regulate Arg homeostasis and ADI-PEG20 sensitivity. These pathways provide potential targets for improving the efficacy of treating Arg-auxotrophic tumors using Arg-deprivation strategies.
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Registered trials
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