ArticleNature2017
CPS1 maintains pyrimidine pools and DNA synthesis in KRAS/LKB1-mutant lung cancer cells.
Article in Nature, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 230 papers, 1 of them a synthesis that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
230 citing papers in PubMed, 1 synthesis or guideline pooled it, 306 citations in OpenAlex.
- Current hotspots and trends in cancer metabolic reprogramming: a scientometric analysis.Frontiers in immunology · 2024Pooled it
- Does Tumor FDG-PET Avidity Represent Enhanced Glycolytic Metabolism in Non-Small Cell Lung Cancer?The Annals of thoracic surgery · 2020Trial
- Neurotransmitter receptor-associated gene signature: prognostic and immunosuppressive microenvironment in NSCLC.Future science OA · 2026Article
- Lung cancer metabolism: a dynamic and adaptive network.Cellular and molecular life sciences : CMLS · 2026Review
- Molecular insights and therapeutic implications for the tumor suppressor role of LKB1 in non-small cell lung cancer.Cancer letters · 2026Review
- Microenvironment-derived acetylated amino acids promote glioblastoma treatment resistance.Research square · 2026Article
- Targeting LKB1-inactivated lung cancers with a stapled peptide inhibitor of the CRTC-CREB pathway.Molecular therapy. Oncology · 2026Article
- CPS1: a multipurpose mitochondrial enzyme, bile protein, acute liver injury biomarker, and cytokine.Gut · 2026Review
- Review
- Stable Isotope-Resolved Metabolomics in Elucidating Mitochondrial Metabolic Reprogramming and Therapeutic Targets.Biomedical chromatography : BMC · 2026Review
- ASS1-derived argininosuccinate promotes purine nucleoside synthesis in B cell acute lymphoblastic leukaemia.Nature metabolism · 2026Article
- Dynamic control of nucleotide metabolism in physiology and disease.Nature cell biology · 2026Review
- Bioengineered systems to exploit tumor microenvironment metabolism.Trends in cancer · 2026Review
- The Role of Urea Cycle Functional Studies in Preclinical Research.Journal of inherited metabolic disease · 2026Review
- ABCC2 as a novel therapeutic target in lung adenocarcinoma: a machine learning-driven discovery linking ammonia metabolism to prognosis and drug resistance.Journal of translational medicine · 2026Article
- Leveraging mitochondrial dynamics-related risk signatures to predict the prognosis and tumor microenvironment of lung adenocarcinoma.Discover oncology · 2026Article
- Acquired resistance of cancer therapies: Mechanisms and perspectives.Chinese medical journal · 2026Review
- Nitrogen metabolism profiling reveals cell state-specific pyrimidine synthesis pathway choice.Nature metabolism · 2026Article
- Reprogramming of nitrogen metabolism in tumors: mechanisms and therapeutic implications.Amino acids · 2026Review
- Nitrogen Isotope Effects in Urea Metabolism: From Biochemistry toInternational journal of molecular sciences · 2026Review
170 more citing papers are in PubMed but not listed here.
Corrections and comments
- Erratum issued
Authors and funding
26 authors at 7 institutions in 2 countries.
Funding
Abstract
Metabolic reprogramming by oncogenic signals promotes cancer initiation and progression. The oncogene KRAS and tumour suppressor STK11, which encodes the kinase LKB1, regulate metabolism and are frequently mutated in non-small-cell lung cancer (NSCLC). Concurrent occurrence of oncogenic KRAS and loss of LKB1 (KL) in cells specifies aggressive oncological behaviour. Here we show that human KL cells and tumours share metabolomic signatures of perturbed nitrogen handling. KL cells express the urea cycle enzyme carbamoyl phosphate synthetase-1 (CPS1), which produces carbamoyl phosphate in the mitochondria from ammonia and bicarbonate, initiating nitrogen disposal. Transcription of CPS1 is suppressed by LKB1 through AMPK, and CPS1 expression correlates inversely with LKB1 in human NSCLC. Silencing CPS1 in KL cells induces cell death and reduces tumour growth. Notably, cell death results from pyrimidine depletion rather than ammonia toxicity, as CPS1 enables an unconventional pathway of nitrogen flow from ammonia into pyrimidines. CPS1 loss reduces the pyrimidine to purine ratio, compromises S-phase progression and induces DNA-polymerase stalling and DNA damage. Exogenous pyrimidines reverse DNA damage and rescue growth. The data indicate that the KL oncological genotype imposes a metabolic vulnerability related to a dependence on a cross-compartmental pathway of pyrimidine metabolism in an aggressive subset of NSCLC.
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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.