ArticleNature metabolism2023
Inhibition of the proline metabolism rate-limiting enzyme P5CS allows proliferation of glutamine-restricted cancer cells.
Article in Nature metabolism, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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
24 citing papers in PubMed, 32 citations in OpenAlex.
- Integrating virtual screening and molecular dynamics simulations to identify emodin as a PYCR1 inhibitor modulating docetaxel sensitivity in prostate cancer.Journal of enzyme inhibition and medicinal chemistry · 2026Article
- Glutamine Metabolism in Health and Diseases.MedComm · 2026Review
- CRISPR-Cas9-producing probiotic bacteria for editing NOX2/gp91Cell reports. Medicine · 2026Article
- ALDH18A1 silencing inhibits lung adenocarcinoma progression through mitochondrial dysfunction and PPAR signaling pathway activation.Biology direct · 2026Article
- Deciphering glutamine metabolic reprogramming: a novel therapeutic target ALDH18A1 in triple-negative breast cancer.Scientific reports · 2026Article
- P5CS-coupled proline metabolism manipulates metabolic dysfunction-associated steatotic liver disease.Life metabolism · 2026Article
- Glutamine metabolism reprogramming promotes bladder cancer progression via PYCR1: a multi-omics and functional validation study.Journal of translational medicine · 2025Article
- Emerging Roles of De Novo Proline Biosynthesis in Human Diseases.FASEB bioAdvances · 2025Review
- Proline Metabolism in Cancer: Emerging Roles in Redox Homeostasis and Therapeutic Opportunities.Cancers · 2025Review
- Prognostic signature and tumor microenvironment infiltration based on amino acid metabolism-related genes and lncRNAs of colorectal cancer.Scientific reports · 2025Article
- Article
- Integrated spatial omics of metabolic reprogramming and the tumor microenvironment in pancreatic cancer.iScience · 2025Article
- Metabolomic reprogramming of the tumor microenvironment by dual arginase inhibitor OATD-02 boosts anticancer immunity.Scientific reports · 2025Article
- Arginine: at the crossroads of nitrogen metabolism.The EMBO journal · 2025Review
- Inhibition of glutathione peroxidase 4 suppresses gastric cancer peritoneal metastasis via regulation of RCC2 homeostasis.Redox biology · 2025Article
- Glutamine and cancer: metabolism, immune microenvironment, and therapeutic targets.Cell communication and signaling : CCS · 2025Review
- Article
- Glutamine Metabolism and Prostate Cancer.Cancers · 2024Review
- Article
- Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
22 authors at 7 institutions in 4 countries.
Funding
Abstract
Glutamine is a critical metabolite for rapidly proliferating cells as it is used for the synthesis of key metabolites necessary for cell growth and proliferation. Glutamine metabolism has been proposed as a therapeutic target in cancer and several chemical inhibitors are in development or in clinical trials. How cells subsist when glutamine is limiting is poorly understood. Here, using an unbiased screen, we identify ALDH18A1, which encodes P5CS, the rate-limiting enzyme in the proline biosynthetic pathway, as a gene that cells can downregulate in response to glutamine starvation. Notably, P5CS downregulation promotes de novo glutamine synthesis, highlighting a previously unrecognized metabolic plasticity of cancer cells. The glutamate conserved from reducing proline synthesis allows cells to produce the key metabolites necessary for cell survival and proliferation under glutamine-restricted conditions. Our findings reveal an adaptive pathway that cancer cells acquire under nutrient stress, identifying proline biosynthesis as a previously unrecognized major consumer of glutamate, a pathway that could be exploited for developing effective metabolism-driven anticancer therapies.
Indexed as
Identifiers
What OpenQuestion holds
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.