ArticleMolecular metabolism2024
Loss of mitochondrial pyruvate carrier 1 supports proline-dependent proliferation and collagen biosynthesis in ovarian cancer.
Article in Molecular metabolism, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.
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Who cites it
7 citing papers in PubMed, 8 citations in OpenAlex.
- Polymorphisms inAnimals : an open access journal from MDPI · 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
- Functional cooperation between the B-cell receptor and NOTCH1 in regulating metabolic reprogramming in chronic lymphocytic leukemia.Leukemia · 2026Article
- Subcellular Stress Markers in Epithelial Ovarian Cancer.International journal of molecular sciences · 2025Review
- Proline Metabolism in Cancer: Emerging Roles in Redox Homeostasis and Therapeutic Opportunities.Cancers · 2025Review
- Pooled CRISPR screens identifies key regulators of bovine stem cell expansion for cultured meat.Communications biology · 2025Article
- Unlocking the mitochondrial functional code: unraveling the pathogenesis of ovarian cancer and innovative targets to inhibit malignant behavior.Journal of translational medicine · 2025Review
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Authors and funding
15 authors at 3 institutions in 1 country.
Funding
Abstract
The pyruvate transporter MPC1 (mitochondrial pyruvate carrier 1) acts as a tumour-suppressor, loss of which correlates with a pro-tumorigenic phenotype and poor survival in several tumour types. In high-grade serous ovarian cancers (HGSOC), patients display copy number loss of MPC1 in around 78% of cases and reduced MPC1 mRNA expression. To explore the metabolic effect of reduced expression, we demonstrate that depleting MPC1 in HGSOC cell lines drives expression of key proline biosynthetic genes; PYCR1, PYCR2 and PYCR3, and biosynthesis of proline. We show that altered proline metabolism underpins cancer cell proliferation, reactive oxygen species (ROS) production, and type I and type VI collagen formation in ovarian cancer cells. Furthermore, exploring The Cancer Genome Atlas, we discovered the PYCR3 isozyme to be highly expressed in a third of HGSOC patients, which was associated with more aggressive disease and diagnosis at a younger age. Taken together, our study highlights that targeting proline metabolism is a potential therapeutic avenue for the treatment of HGSOC.
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Registered trials
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