ArticleThe Journal of biological chemistry2016
Aspartate Rescues S-phase Arrest Caused by Suppression of Glutamine Utilization in KRas-driven Cancer Cells.
Article in The Journal of biological chemistry, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 52 papers.
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Who cites it
52 citing papers in PubMed, 87 citations in OpenAlex.
- Aspartate Transporter SLC1A3 Promotes Colorectal Cancer via MDM2-p53 Pathway and M2 Macrophage Polarization.Cancer science · 2026Article
- Nitrogen Isotope Effects in Urea Metabolism: From Biochemistry toInternational journal of molecular sciences · 2026Review
- Intestinal Multi-Target Mechanisms of Natural Active Substances in Hyperuricemia Alleviation: Recent Progress.Nutrients · 2026Review
- KCTD10 as a selective cancer dependency from transcription-replication conflicts (TRCs).Ageing and cancer research & treatment · 2026Article
- Complex interactions of gut-derived short-chain fatty acids in hyperuricemia and gout pathophysiology.Frontiers in microbiology · 2026Review
- Untargeted Metabolomics Reveals Distinct Serum Metabolic Profiles in Avian Influenza Occupational Exposure Populations.Metabolites · 2025Article
- Beyond the tumor: Enhancing pancreatic cancer therapy through glutamine metabolism and innovative drug delivery.Journal of cell communication and signaling · 2025Review
- Review
- Metabolic Adaptations in Cancer Progression: Optimization Strategies and Therapeutic Targets.Cancers · 2025Review
- The metabolism-immune axis in colorectal cancer: remodeling the tumor microenvironment through metabolite signaling.Frontiers in immunology · 2025Review
- Natural products as metabolic modulators to enhance cancer immunotherapy: reprogramming the tumor microenvironment.Frontiers in immunology · 2025Review
- Article
- Amino acid metabolism in tumor biology and therapy.Cell death & disease · 2024Review
- Glutamine addiction in tumor cell: oncogene regulation and clinical treatment.Cell communication and signaling : CCS · 2024Review
- An engineered biosensor enables dynamic aspartate measurements in living cells.bioRxiv : the preprint server for biology · 2023Article
- SLC25A21 downregulation promotes KRAS-mutant colorectal cancer progression by increasing glutamine anaplerosis.JCI insight · 2023Article
- Selenium deficiency-induced multiple tissue damage with dysregulation of immune and redox homeostasis in broiler chicks under heat stress.Science China. Life sciences · 2023Article
- Targeting glutaminase is therapeutically effective in ibrutinib-resistant mantle cell lymphoma.Haematologica · 2023Article
- The mitochondrial CabioRxiv : the preprint server for biology · 2023Article
- The mitochondrial CaFrontiers in cell and developmental biology · 2023Article
Corrections and comments
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Authors and funding
7 authors at 3 institutions in 1 country.
Funding
Abstract
During G1-phase of the cell cycle, normal cells respond first to growth factors that indicate that it is appropriate to divide and then later in G1 to the presence of nutrients that indicate sufficient raw material to generate two daughter cells. Dividing cells rely on the "conditionally essential" amino acid glutamine (Q) as an anaplerotic carbon source for TCA cycle intermediates and as a nitrogen source for nucleotide biosynthesis. We previously reported that while non-transformed cells arrest in the latter portion of G1 upon Q deprivation, mutant KRas-driven cancer cells bypass the G1 checkpoint, and instead, arrest in S-phase. In this study, we report that the arrest of KRas-driven cancer cells in S-phase upon Q deprivation is due to the lack of deoxynucleotides needed for DNA synthesis. The lack of deoxynucleotides causes replicative stress leading to activation of the ataxia telangiectasia and Rad3-related protein (ATR)-mediated DNA damage pathway, which arrests cells in S-phase. The key metabolite generated from Q utilization was aspartate, which is generated from a transaminase reaction whereby Q-derived glutamate is converted to α-ketoglutarate with the concomitant conversion of oxaloacetate to aspartate. Aspartate is a critical metabolite for both purine and pyrimidine nucleotide biosynthesis. This study identifies the molecular basis for the S-phase arrest caused by Q deprivation in KRas-driven cancer cells that arrest in S-phase in response to Q deprivation. Given that arresting cells in S-phase sensitizes cells to apoptotic insult, this study suggests novel therapeutic approaches to KRas-driven cancers.
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Registered trials
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.