ArticlePloS one2022
Increased mitochondrial proline metabolism sustains proliferation and survival of colorectal cancer cells.
Article in PloS one, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed, 26 citations in OpenAlex.
- Deciphering glutamine metabolic reprogramming: a novel therapeutic target ALDH18A1 in triple-negative breast cancer.Scientific reports · 2026Article
- Extracellular Vesicles fromNanomaterials (Basel, Switzerland) · 2026Article
- [Research Progress on the Role and Mechanisms of PYCR1 in Tumorigenesis and Progression].Zhongguo fei ai za zhi = Chinese journal of lung cancer · 2026Review
- LINC02878/ZNF282/PYCR2 axis promotes proline synthesis and tumor progression in colorectal cancer.Cellular and molecular life sciences : CMLS · 2025Article
- Proline Metabolism in Cancer: Emerging Roles in Redox Homeostasis and Therapeutic Opportunities.Cancers · 2025Review
- Making sense of human colorectal cancer molecular subtypes: mice are stepping in.Cell death discovery · 2025Article
- Understanding disease-associated metabolic changes in human colonic epithelial cells using the iColonEpithelium metabolic reconstruction.PLoS computational biology · 2025Article
- Effect and mechanism of PYCR1 on biological function of hepatocellular carcinoma cells under hypoxia.Discover oncology · 2025Article
- Novel machine-learning bioinformatics reveal distinct metabolic alterations for enhanced colorectal cancer diagnosis and monitoring.iMetaOmics · 2025Article
- Identification of fatty acid anabolism patterns to predict prognosis and immunotherapy response in gastric cancer.Discover oncology · 2025Article
- Screening a knowledge-based library of low molecular weight compounds against the proline biosynthetic enzyme 1-pyrroline-5-carboxylate 1 (PYCR1).Protein science : a publication of the Protein Society · 2024Article
- Novel Fragment Inhibitors of PYCR1 from Docking-Guided X-ray Crystallography.Journal of chemical information and modeling · 2024Article
- Loss of mitochondrial pyruvate carrier 1 supports proline-dependent proliferation and collagen biosynthesis in ovarian cancer.Molecular metabolism · 2024Article
- BRAFCommunications biology · 2023Article
- SLC25A51 promotes tumor growth through sustaining mitochondria acetylation homeostasis and proline biogenesis.Cell death and differentiation · 2023Article
- Functional Impact of a Cancer-Related Variant in Human ΔACS omega · 2023Article
- Roles of circRNA dysregulation in esophageal squamous cell carcinoma tumor microenvironment.Frontiers in oncology · 2023Review
- Transcriptome and co-expression network analysis reveals the molecular mechanism of inosine monophosphate-specific deposition in chicken muscle.Frontiers in physiology · 2023Article
- Identification of functional gene modules by integrating multi-omics data and known molecular interactions.Frontiers in genetics · 2023Article
- Circ_0000705 facilitates proline metabolism of esophageal squamous cell carcinoma cells by targeting miR-621/PYCR1 axis.Discover oncology · 2022Article
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Authors and funding
18 authors at 2 institutions in 2 countries.
Funding
Abstract
Research into the metabolism of the non-essential amino acid (NEAA) proline in cancer has gained traction in recent years. The last step in the proline biosynthesis pathway is catalyzed by pyrroline-5-carboxylate reductase (PYCR) enzymes. There are three PYCR enzymes: mitochondrial PYCR1 and 2 and cytosolic PYCR3 encoded by separate genes. The expression of the PYCR1 gene is increased in numerous malignancies and correlates with poor prognosis. PYCR1 expression sustains cancer cells' proliferation and survival and several mechanisms have been implicated to explain its oncogenic role. It has been suggested that the biosynthesis of proline is key to sustain protein synthesis, support mitochondrial function and nucleotide biosynthesis. However, the links between proline metabolism and cancer remain ill-defined and are likely to be tissue specific. Here we use a combination of human dataset, human tissue and mouse models to show that the expression levels of the proline biosynthesis enzymes are significantly increased during colorectal tumorigenesis. Functionally, the expression of mitochondrial PYCRs is necessary for cancer cells' survival and proliferation. However, the phenotypic consequences of PYCRs depletion could not be rescued by external supplementation with either proline or nucleotides. Overall, our data suggest that, despite the mechanisms underlying the role of proline metabolism in colorectal tumorigenesis remain elusive, targeting the proline biosynthesis pathway is a suitable approach for the development of novel anti-cancer therapies.
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