ArticleNature2016
Tumour-specific proline vulnerability uncovered by differential ribosome codon reading.
Article in Nature, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 176 papers.
What it found
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Who cites it
176 citing papers in PubMed, 278 citations in OpenAlex.
- Translational resistance to amino acid starvation in breast cancer cells revealed by ribosome profiling.iScience · 2026Article
- Arginine Deprivation of ASS1-Deficient Cancers Drives Mistranslation and Shared Neoepitope Production.Cancer research · 2026Article
- Targeting non-canonical antigens unlocks functional T-cell responses in renal cell carcinoma.Journal for immunotherapy of cancer · 2026Article
- Human SRD5A1 as a case of gene expression indel-resistance in triple-coding region.Genome biology · 2026Article
- Targeting a Unique Cysteine Residue to Achieve Isoform-Selective Inhibition of the Proline Biosynthetic Enzyme Pyrroline-5-Carboxylate Reductase 2.ACS chemical biology · 2026Article
- Type II tRNA cleavage by SLFN14 endoribonuclease variants linked to inherited thrombocytopenia drives global translational repression.PLoS biology · 2026Article
- S6K1 overexpression enhances autophagy in breast cancer cells by inducing the translation of CLU.Chinese medical journal · 2026Article
- Single cell and multi-omics analysis reveal senescence-related molecular subtypes and a prognostic signature in clear cell renal cell carcinoma.Discover oncology · 2026Article
- Ribosome Homeostasis Regulated by SETD2 Preserves Intestinal Epithelial Barrier.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Targeting tRNA-Arg-TCT-4-1 suppresses cancer cell growth and tumorigenesis.bioRxiv : the preprint server for biology · 2026Article
- ALDH2/eIF3E Interaction Modulates Protein Translation Critical for Cardiomyocyte Ferroptosis in Acute Myocardial Ischemia Injury.Circulation · 2026Article
- Ribosome-associated quality control of aberrant protein production during amino acid limitation.bioRxiv : the preprint server for biology · 2026Article
- The key enzyme PYCR1 in proline metabolism: a dual driver of cancer progression and fibrotic remodeling.Journal of enzyme inhibition and medicinal chemistry · 2025Review
- Hypoxia-induced PYCR1 regulates glycolysis and histone lactylation to promote bladder cancer progression and metastasis via SLC6A14/Glutamine metabolism.Cancer biology & therapy · 2025Article
- Serine tRNAs compete to regulate the mRNA translation of serine-sensitive codons.Science advances · 2025Article
- Cancer progression through the lens of age-induced metabolic reprogramming.Nature reviews. Cancer · 2025Review
- Proline Metabolism in Cancer: Emerging Roles in Redox Homeostasis and Therapeutic Opportunities.Cancers · 2025Review
- Oncogenic roles of young human de novo genes and their potential as neoantigens in cancer immunotherapy.Cell genomics · 2025Article
- Interpreting ribosome dynamics during mRNA translation.The Journal of biological chemistry · 2025Review
- Amino acids shape the metabolic and immunologic landscape in the tumor immune microenvironment: from molecular mechanisms to therapeutic strategies.Cancer biology & medicine · 2025Review
116 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
13 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Tumour growth and metabolic adaptation may restrict the availability of certain amino acids for protein synthesis. It has recently been shown that certain types of cancer cells depend on glycine, glutamine, leucine and serine metabolism to proliferate and survive. In addition, successful therapies using L-asparaginase-induced asparagine deprivation have been developed for acute lymphoblastic leukaemia. However, a tailored detection system for measuring restrictive amino acids in each tumour is currently not available. Here we harness ribosome profiling for sensing restrictive amino acids, and develop diricore, a procedure for differential ribosome measurements of codon reading. We first demonstrate the functionality and constraints of diricore using metabolic inhibitors and nutrient deprivation assays. Notably, treatment with L-asparaginase elicited both specific diricore signals at asparagine codons and high levels of asparagine synthetase (ASNS). We then applied diricore to kidney cancer and discover signals indicating restrictive proline. As for asparagine, this observation was linked to high levels of PYCR1, a key enzyme in proline production, suggesting a compensatory mechanism allowing tumour expansion. Indeed, PYCR1 is induced by shortage of proline precursors, and its suppression attenuated kidney cancer cell proliferation when proline was limiting. High PYCR1 is frequently observed in invasive breast carcinoma. In an in vivo model system of this tumour, we also uncover signals indicating restrictive proline. We further show that CRISPR-mediated knockout of PYCR1 impedes tumorigenic growth in this system. Thus, diricore has the potential to reveal unknown amino acid deficiencies, vulnerabilities that can be used to target key metabolic pathways for cancer treatment.
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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.