ArticleMolecular cancer2009
Overexpression of RRM2 decreases thrombspondin-1 and increases VEGF production in human cancer cells in vitro and in vivo: implication of RRM2 in angiogenesis.
Article in Molecular cancer, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 65 papers, 1 of them a synthesis that pooled it.
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Who cites it
65 citing papers in PubMed, 1 synthesis or guideline pooled it, 100 citations in OpenAlex.
- Prognostic and therapeutic significance of ribonucleotide reductase small subunit M2 in estrogen-negative breast cancers.BMC cancer · 2014Pooled it
- Ribonucleotide reductase (RNR) inhibitors as target-based weapon for future cancer drug development.Future medicinal chemistry · 2025Review
- Ribonucleotide-diphosphate reductase subunit M2 (RRM2) expression and colorectal cancer invasiveness: a potential prognostic biomarker.Molecular biology reports · 2025Article
- Tumoroid Model Reveals Synergistic Impairment of Metabolism by Iron Chelators and Temozolomide in Chemo-Resistant Patient-derived Glioblastoma Cells.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Ribonucleotide reductase small subunit M2 promotes the proliferation of esophageal squamous cell carcinoma cellsActa pharmaceutica Sinica. B · 2024Article
- Exosomes: a review of biologic function, diagnostic and targeted therapy applications, and clinical trials.Journal of biomedical science · 2024Review
- Machine learning and weighted gene co-expression network analysis identify a three-gene signature to diagnose rheumatoid arthritis.Frontiers in immunology · 2024Article
- Targeting of RRM2 suppresses DNA damage response and activates apoptosis in atypical teratoid rhabdoid tumor.Journal of experimental & clinical cancer research : CR · 2023Article
- Inhibition of USP7 upregulates USP22 and activates its downstream cancer-related signaling pathways in human cancer cells.Cell communication and signaling : CCS · 2023Article
- Network Pharmacology and Bioinformatics Study of Geniposide Regulating Oxidative Stress in Colorectal Cancer.International journal of molecular sciences · 2023Article
- Prognostic and Immunological Potential of Ribonucleotide Reductase Subunits in Liver Cancer.Oxidative medicine and cellular longevity · 2023Article
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- Inhibitors of the Cancer Target Ribonucleotide Reductase, Past and Present.Biomolecules · 2022Review
- Exploring Potential Biomarkers, Ferroptosis Mechanisms, and Therapeutic Targets Associated with Cutaneous Squamous Cell Carcinoma via Integrated Transcriptomic Analysis.Journal of healthcare engineering · 2022Article
- Still no Rest for the Reductases: Ribonucleotide Reductase (RNR) Structure and Function: An Update.Sub-cellular biochemistry · 2022Review
- Derangement of cell cycle markers in peripheral blood mononuclear cells of asthmatic patients as a reliable biomarker for asthma control.Scientific reports · 2021Article
- MicroRNA-20a-5p suppresses tumor angiogenesis of non-small cell lung cancer through RRM2-mediated PI3K/Akt signaling pathway.Molecular and cellular biochemistry · 2021Article
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- Anti-Tumor Effect of Apatinib and Relevant Mechanisms in Liposarcoma.Frontiers in oncology · 2021Article
5 more citing papers are in PubMed but not listed here.
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Authors and funding
9 authors at 1 institution in 1 country.
Funding
Abstract
backgroundIn addition to its essential role in ribonucleotide reduction, ribonucleotide reductase (RNR) small subunit, RRM2, has been known to play a critical role in determining tumor malignancy. Overexpression of RRM2 significantly enhances the invasive and metastatic potential of tumor. Angiogenesis is critical to tumor malignancy; it plays an essential role in tumor growth and metastasis. It is important to investigate whether the angiogenic potential of tumor is affected by RRM2.
resultsWe examined the expression of antiangiogenic thrombospondin-1 (TSP-1) and proangiogenic vascular endothelial growth factor (VEGF) in two RRM2-overexpressing KB cells: KB-M2-D and KB-HURs. We found that TSP-1 was significantly decreased in both KB-M2-D and KB-HURs cells compared to the parental KB and mock transfected KB-V. Simultaneously, RRM2-overexpressing KB cells showed increased production of VEGF mRNA and protein. In contrast, attenuating RRM2 expression via siRNA resulted in a significant increased TSP-1 expression in both KB and LNCaP cells; while the expression of VEGF by the two cells was significantly decreased under both normoxia and hypoxia. In comparison with KB-V, overexpression of RRM2 had no significant effect on proliferation in vitro, but it dramatically accelerated in vivo subcutaneous growth of KB-M2-D. KB-M2-D possessed more angiogenic potential than KB-V, as shown in vitro by its increased chemotaxis for endothelial cells and in vivo by the generation of more vascularized tumor xenografts.
conclusionThese findings suggest a positive role of RRM2 in tumor angiogenesis and growth through regulation of the expression of TSP-1 and VEGF.
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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.