ArticleScientific reports2015
Proline biosynthesis augments tumor cell growth and aerobic glycolysis: involvement of pyridine nucleotides.
Article in Scientific reports, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 112 papers.
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Who cites it
112 citing papers in PubMed, 166 citations in OpenAlex.
- Targeting a Unique Cysteine Residue to Achieve Isoform-Selective Inhibition of the Proline Biosynthetic Enzyme Pyrroline-5-Carboxylate Reductase 2.ACS chemical biology · 2026Article
- Single cell and multi-omics analysis reveal senescence-related molecular subtypes and a prognostic signature in clear cell renal cell carcinoma.Discover oncology · 2026Article
- Proline Metabolism in Cancer: Emerging Roles in Redox Homeostasis and Therapeutic Opportunities.Cancers · 2025Review
- HOGA1 Suppresses Renal Cell Carcinoma Growth via Inhibiting the Wnt/β-Catenin Signalling Pathway.Journal of cellular and molecular medicine · 2025Article
- Metabolomic characterisation of the glioblastoma invasive margin reveals a region-specific signature.Heliyon · 2025Article
- Metabolic Reprogramming at the Edge of Redox: Connections Between Metabolic Reprogramming and Cancer Redox State.International journal of molecular sciences · 2025Review
- The new insight into the role of hydroxyproline in metabolism of cancer cells.Frontiers in cell and developmental biology · 2025Review
- Molecular subtyping and functional characterization of gastric cancer using arginine metabolism-related genes.Frontiers in cell and developmental biology · 2025Article
- Targeting the glutamine-arginine-proline metabolism axis in cancer.Journal of enzyme inhibition and medicinal chemistry · 2024Review
- Deubiquitinase USP9x regulates the proline biosynthesis pathway in non-small cell lung cancer.Cell death discovery · 2024Article
- Article
- MYC Oncogene: A Druggable Target for Treating Cancers with Natural Products.Aging and disease · 2024Review
- Loss of mitochondrial pyruvate carrier 1 supports proline-dependent proliferation and collagen biosynthesis in ovarian cancer.Molecular metabolism · 2024Article
- Integrated Network Pharmacology and Metabolomics to Dissect the Mechanisms of Naringin for Treating Cervical Cancer.Combinatorial chemistry & high throughput screening · 2024Article
- Transcriptomic Analysis of Cardiac Tissues in a Rodent Model of Coronary Microembolization.Journal of inflammation research · 2024Article
- Inhibition of the proline metabolism rate-limiting enzyme P5CS allows proliferation of glutamine-restricted cancer cells.Nature metabolism · 2023Article
- Acid-base Homeostasis and Implications to the Phenotypic Behaviors of Cancer.Genomics, proteomics & bioinformatics · 2023Article
- Photosynthesis regulation, cell membrane stabilization and methylglyoxal detoxification seems major altered pathways under cold stress as revealed by integrated multi-omics meta-analysis.Physiology and molecular biology of plants : an international journal of functional plant biology · 2023Article
- Proline pre-conditioning of Jurkat cells improves recovery after cryopreservation.RSC medicinal chemistry · 2023Article
- Unraveling the Mechanisms of Ch-SeNP Cytotoxicity against Cancer Cells: Insights from Targeted and Untargeted Metabolomics.Nanomaterials (Basel, Switzerland) · 2023Article
52 more citing papers are in PubMed but not listed here.
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Authors and funding
5 authors at 3 institutions in 1 country.
Funding
Abstract
The metabolism of the nonessential amino acid proline contributes to tumor metabolic reprogramming. Previously we showed that MYC increases proline biosynthesis (PB) from glutamine. Here we show MYC increases the expression of the enzymes in PB at both protein and mRNA levels. Blockade of PB decreases tumor cell growth and energy production. Addition of Δ(1)-pyrroline-5-carboxylate (P5C) or proline reverses the effects of P5C synthase knockdown but not P5C reductases knockdown. Importantly, the reversal effect of proline was blocked by concomitant proline dehydrogenase/oxidase (PRODH/POX) knockdown. These findings suggest that the important regulatory contribution of PB to tumor growth derives from metabolic cycling between proline and P5C rather than product proline or intermediate P5C. We further document the critical role of PB in maintaining pyridine nucleotide levels by connecting the proline cycle to glycolysis and to the oxidative arm of the pentose phosphate pathway. These findings establish a novel function of PB in tumorigenesis, linking the reprogramming of glucose, glutamine and pyridine nucleotides, and may provide a novel target for antitumor therapy.
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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.