ArticleNature metabolism2022
Cancer-associated fibroblasts require proline synthesis by PYCR1 for the deposition of pro-tumorigenic extracellular matrix.
Article in Nature metabolism, 2022. 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 115 papers.
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Who cites it
115 citing papers in PubMed, 141 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
- Metabolites and cancer metastasis.Oncogene · 2026Review
- Metabolic reprogramming in cancer-associated fibroblasts: orchestrating the tumor immune microenvironment and response to immune checkpoint blockade.Experimental hematology & oncology · 2026Review
- Beyond the Monolayer: Leveraging 3D Culture Systems to Decode Mechanisms of Drug Resistance and Therapeutic Vulnerabilities in Colorectal Cancer.Cancer medicine · 2026Review
- Pyrroline-5-carboxylate reductase 1 interacts with Nudix hydrolase 5 to drive bladder cancer malignant progression via activation of the APOE/JAK2/STAT3 signalling axis.Clinical and translational medicine · 2026Article
- Branched-chain amino acid transaminase 1-mediated pathway promotes proline-dependent collagen production in cardiac myofibroblasts.The Journal of clinical investigation · 2026Article
- Fueling fibrosis: BCAT1 links branched-chain amino acid metabolism to collagen production.The Journal of clinical investigation · 2026Article
- Unraveling the role of glutamine metabolism in cancer: from cell death mechanisms to tumor microenvironment modulation.Experimental hematology & oncology · 2026Review
- CRISPR-Cas9-producing probiotic bacteria for editing NOX2/gp91Cell reports. Medicine · 2026Article
- MYCN-driven metabolic remodelling of the tumour microenvironment in neuroblastoma: implications for stromal biology and CAF heterogeneity.Cancer metastasis reviews · 2026Review
- Immunomodulation by collagen VI across fibrotic and tumor microenvironmental contexts.Histology and histopathology · 2026Review
- PYCR1 modulates ferroptosis and malignant phenotypes of clear cell renal cell carcinoma through proline biosynthesis.Molecular biology reports · 2026Article
- Mitochondrial NADK2-dependent NADPH controls tau oligomer uptake in human neurons.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026Article
- Cancer stem cells synthesize proline to attenuate oxidative stress.The Journal of clinical investigation · 2026Article
- Region-Resolved Integrative Multi-Omic Characterization Reveals Diverse Tumor and Microenvironment Features of Pituitary Neuroendocrine Tumors.Molecular & cellular proteomics : MCP · 2026Article
- Amino Acids as Targets for Immunotherapy against Solid Tumors.Cell biochemistry and biophysics · 2026Review
- Article
- Integration of a glutamine metabolism-based prognostic signature and a synergistic nanotherapeutic strategy targeting metabolic vulnerabilities in prostate cancer.Discover oncology · 2026Article
- Metabolic networks in the tumor microenvironment: roles of amino acid and lipid metabolism pathways in cancer progression and therapy.Experimental & molecular medicine · 2026Review
- Cancer-Associated Fibroblasts Functions as Multifunctional Architects of the Tumor Stroma and Represent Emerging Therapeutic Vulnerabilities.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Review
55 more citing papers are in PubMed but not listed here.
Corrections and comments
- Erratum issued
Authors and funding
29 authors at 7 institutions in 4 countries.
Funding
Abstract
Elevated production of collagen-rich extracellular matrix is a hallmark of cancer-associated fibroblasts (CAFs) and a central driver of cancer aggressiveness. Here we find that proline, a highly abundant amino acid in collagen proteins, is newly synthesized from glutamine in CAFs to make tumour collagen in breast cancer xenografts. PYCR1 is a key enzyme for proline synthesis and highly expressed in the stroma of breast cancer patients and in CAFs. Reducing PYCR1 levels in CAFs is sufficient to reduce tumour collagen production, tumour growth and metastatic spread in vivo and cancer cell proliferation in vitro. Both collagen and glutamine-derived proline synthesis in CAFs are epigenetically upregulated by increased pyruvate dehydrogenase-derived acetyl-CoA levels. PYCR1 is a cancer cell vulnerability and potential target for therapy; therefore, our work provides evidence that targeting PYCR1 may have the additional benefit of halting the production of a pro-tumorigenic extracellular matrix. Our work unveils new roles for CAF metabolism to support pro-tumorigenic collagen production.
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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.