ArticleNature metabolism2021
Fibroblast pyruvate carboxylase is required for collagen production in the tumour microenvironment.
Article in Nature metabolism, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 44 papers.
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The trial behind it
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Who cites it
44 citing papers in PubMed, 74 citations in OpenAlex.
- Macrophage-supported metabolic adaptation drives tumor survival under nutrient stress.Science advances · 2026Article
- Oxygen-dependent subcellular redistribution of PHD3 links the hypoxic microenvironment to mitochondrial metabolic reprogramming in ccRCC.Experimental & molecular medicine · 2026Article
- TGF-β coordinates alanine synthesis and import for myofibroblast differentiation in pulmonary fibrosis.JCI insight · 2026Article
- CIITA/PRMT5 promote CD4BMC medicine · 2026Article
- Glutamine-dependent changes in fibroblast-derived extracellular matrix dictate cancer cell behavior.Matrix biology : journal of the International Society for Matrix Biology · 2026Article
- Activatable NIR Schaap's 1,2-Dioxetane-Based Chemiluminescent Probes for Bioimaging Applications.Chemical & biomedical imaging · 2026Review
- Hepatocyte estrogen-related receptor α modulates a gluconeogenic-epigenetic crosstalk counteracting MASLD/MASH progression.Experimental & molecular medicine · 2026Article
- From Sample to Mixed Reality: A Translational 3D MALDI Imaging Platform for Advanced 3D Spatial Omics Analysis of 3D Cell Culture Disease Models.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Mechanical regulation of metabolism, epigenetics, and their interplay.npj biomedical innovations · 2026Review
- Adipose-derived stem cell peptide 5 alleviates hypertrophic scarring through targeting pyruvate carboxylase or p50 to coordinate PI3K/AKT/mTOR-autophagy and NF-κB/IL-6 signaling.Burns & trauma · 2026Article
- Nanomedicine for targeting cancer-associated fibroblasts in cancer therapy.Theranostics · 2026Review
- Targeting cuproptosis for treatment and prognostic assessment in endometrial cancer.Cancer cell international · 2025Review
- Lactate and lactylation: molecular insights into histone and non-histone lactylation in tumor progression, tumor immune microenvironment, and therapeutic strategies.Biomarker research · 2025Review
- Identification of anoikis-related tumor microenvironment characteristics and prognostic signature in ovarian cancer at bulk and single-cell levels.Discover oncology · 2025Article
- Cancer-associated fibroblasts as mediators of tissue microenvironment remodeling in cancer.Current opinion in cell biology · 2025Review
- Water-Driven Oxygen and Nitric Oxide Release from Porphyrin- and Mn-Based Metal-Organic Framework Enables Accelerated Acute Wound Healing.ACS applied bio materials · 2025Article
- Plasticity and Functional Heterogeneity of Cancer-Associated Fibroblasts.Cancer research · 2025Review
- Pyruvate Carboxylase in Macrophages Aggravates Atherosclerosis by Regulating Metabolism Reprogramming to Promote Inflammatory Responses Through the Hypoxia-Inducible Factor-1 Signaling Pathway.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- The loss of OPA1 accelerates intervertebral disc degeneration and osteoarthritis in aged mice.Nature communications · 2025Article
- Deletion of Pyruvate Carboxylase in Tubular Epithelial Cell Promotes Renal Fibrosis by Regulating SQOR/cGAS/STING-Mediated Glycolysis.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
Abstract
The aberrant production of collagen by fibroblasts is a hallmark of many solid tumours and can influence cancer progression. How the mesenchymal cells in the tumour microenvironment maintain their production of extracellular matrix proteins as the vascular delivery of glutamine and glucose becomes compromised remains unclear. Here we show that pyruvate carboxylase (PC)-mediated anaplerosis in tumour-associated fibroblasts contributes to tumour fibrosis and growth. Using cultured mesenchymal and cancer cells, as well as mouse allograft models, we provide evidence that extracellular lactate can be utilized by fibroblasts to maintain tricarboxylic acid (TCA) cycle anaplerosis and non-essential amino acid biosynthesis through PC activity. Furthermore, we show that fibroblast PC is required for collagen production in the tumour microenvironment. These results establish TCA cycle anaplerosis as a determinant of extracellular matrix collagen production, and identify PC as a potential target to inhibit tumour desmoplasia.
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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.