ArticleJournal of experimental & clinical cancer research : CR2022
Pyrroline-5-Carboxylate Reductase 1: a novel target for sensitizing multiple myeloma cells to bortezomib by inhibition of PRAS40-mediated protein synthesis.
Article in Journal of experimental & clinical cancer research : CR, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
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Who cites it
26 citing papers in PubMed, 30 citations in OpenAlex.
- Activating a novel cell death pathway to target PI-resistant multiple myeloma and enhance immunogenic cell death.Apoptosis : an international journal on programmed cell death · 2026Article
- Cancer stem cells synthesize proline to attenuate oxidative stress.The Journal of clinical investigation · 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
- [Research Progress on the Role and Mechanisms of PYCR1 in Tumorigenesis and Progression].Zhongguo fei ai za zhi = Chinese journal of lung cancer · 2026Review
- PYCR1 inhibition in bone marrow stromal cells enhances bortezomib sensitivity in multiple myeloma cells by altering their metabolism.Molecular oncology · 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
- The regulatory role and mechanism of energy metabolism and immune response in head and neck cancer.Genes & diseases · 2025Review
- Proline Metabolism in Cancer: Emerging Roles in Redox Homeostasis and Therapeutic Opportunities.Cancers · 2025Review
- Syntenin inhibition impairs stroma-tumor communication in multiple myeloma and improves bortezomib treatment efficiency.HemaSphere · 2025Article
- Integrative Analysis of Immune- and Metabolism-Related Genes Identifies Robust Prognostic Signature and PYCR1 as a Carcinogenic Regulator in Clear Cell Renal Cell Carcinoma.International journal of molecular sciences · 2025Article
- Integrated Proteomics and Machine Learning Approach Reveals PYCR1 as a Novel Biomarker to Predict Prognosis of Sinonasal Squamous Cell Carcinoma.International journal of molecular sciences · 2024Article
- Review
- Article
- 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
- Targeting mTOR signaling pathways in multiple myeloma: biology and implication for therapy.Cell communication and signaling : CCS · 2024Review
- PYCR1 regulates TRAIL‑resistance in non‑small cell lung cancer cells by regulating the redistribution of death receptors.Oncology letters · 2024Article
- Novel Fragment Inhibitors of PYCR1 from Docking-Guided X-ray Crystallography.Journal of chemical information and modeling · 2024Article
- Pyrroline-5-carboxylate reductase 1 reprograms proline metabolism to drive breast cancer stemness under psychological stress.Cell death & disease · 2023Article
- Proline is increased in allergic asthma and promotes airway remodeling.JCI insight · 2023Article
- Metabolic Alterations in Multiple Myeloma: From Oncogenesis to Proteasome Inhibitor Resistance.Cancers · 2023Review
Corrections and comments
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Authors and funding
11 authors at 2 institutions in 1 country.
Funding
Abstract
backgroundMultiple myeloma (MM) remains an incurable cancer despite advances in therapy. Therefore, the search for new targets is still essential to uncover potential treatment strategies. Metabolic changes, induced by the hypoxic bone marrow, contribute to both MM cell survival and drug resistance. Pyrroline-5-carboxylate reductase 1 and 2 (PYCR1 and PYCR2) are two mitochondrial enzymes that facilitate the last step in the glutamine-to-proline conversion. Overexpression of PYCR1 is involved in progression of several cancers, however, its' role in hematological cancers is unknown. In this study, we investigated whether PYCR affects MM viability, proliferation and response to bortezomib.
methodsCorrelation of PYCR1/2 with overall survival was investigated in the MMRF CoMMpass trial (653 patients). OPM-2 and RPMI-8226 MM cell lines were used to perform in vitro experiments. RPMI-8226 cells were supplemented with
resultsWe found that PYCR1 and PYCR2 mRNA expression correlated with an inferior overall survival. MM cells from relapsed/refractory patients express significantly higher levels of PYCR1 mRNA. In line with the strong expression of PYCR1, we performed a tracer study in RPMI-8226 cells, which revealed an increased conversion of
conclusionsThis study identifies PYCR1 as a novel target in bortezomib-based combination therapies for MM.
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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 Socratic graph.