ArticleInternational journal of oncology2006
siRNA-mediated simultaneous downregulation of uPA and its receptor inhibits angiogenesis and invasiveness triggering apoptosis in breast cancer cells.
Article in International journal of oncology, 2006. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 papers.
What it found
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Who cites it
37 citing papers in PubMed, 63 citations in OpenAlex.
- Proteomics-Based Soluble Urokinase Plasminogen Activator Receptor Levels and Long-Term Cardiovascular Outcomes in Survivors of Breast Cancer: A UK Biobank Study.Journal of the American Heart Association · 2025Article
- Therapeutic delivery of siRNA for the management of breast cancer and triple-negative breast cancer.Therapeutic delivery · 2024Review
- siRNA and targeted delivery systems in breast cancer therapy.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2023Review
- Urokinase-type plasminogen activator receptor (uPAR) as a therapeutic target in cancer.Journal of translational medicine · 2022Review
- Urokinase Receptor uPAR Downregulation in Neuroblastoma Leads to Dormancy, Chemoresistance and Metastasis.Cancers · 2022Article
- Modulation of Cellular Function by the Urokinase Receptor Signalling: A Mechanistic View.Frontiers in cell and developmental biology · 2022Review
- Fibrinolytic System and Cancer: Diagnostic and Therapeutic Applications.International journal of molecular sciences · 2021Review
- Plasmin and Plasminogen System in the Tumor Microenvironment: Implications for Cancer Diagnosis, Prognosis, and Therapy.Cancers · 2021Review
- Improved therapeutic efficacy of quercetin-loaded polymeric nanoparticles on triple-negative breast cancer by inhibiting uPA.RSC advances · 2020Article
- Endothelial YAP/TAZ Signaling in Angiogenesis and Tumor Vasculature.Frontiers in oncology · 2020Review
- Suppression of Urokinase-Type Plasminogen Activator Receptor by Docosahexaenoic Acid Mediated by Heme Oxygenase-1 in 12-Frontiers in pharmacology · 2020Article
- Multifaceted Role of the Urokinase-Type Plasminogen Activator (uPA) and Its Receptor (uPAR): Diagnostic, Prognostic, and Therapeutic Applications.Frontiers in oncology · 2018Review
- Urokinase plasminogen activator protects cardiac myocytes from oxidative damage and apoptosis via hOGG1 induction.Apoptosis : an international journal on programmed cell death · 2017Article
- uPAR enhances malignant potential of triple-negative breast cancer by directly interacting with uPA and IGF1R.BMC cancer · 2016Article
- Cyr61 and YB-1 are novel interacting partners of uPAR and elevate the malignancy of triple-negative breast cancer.Oncotarget · 2016Article
- Additive impact of HER2-/PTK6-RNAi on interactions with HER3 or IGF-1R leads to reduced breast cancer progression in vivo.Molecular oncology · 2015Article
- Plasminogen activator urokinase expression reveals TRAIL responsiveness and supports fractional survival of cancer cells.Cell death & disease · 2014Article
- Effects of miR-193a and sorafenib on hepatocellular carcinoma cells.Molecular cancer · 2013Article
- Probing binding and cellular activity of pyrrolidinone and piperidinone small molecules targeting the urokinase receptor.ChemMedChem · 2013Article
- Small-molecule inhibition of the uPAR·uPA interaction: synthesis, biochemical, cellular, in vivo pharmacokinetics and efficacy studies in breast cancer metastasis.Bioorganic & medicinal chemistry · 2013Article
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 2 countries.
Funding
Abstract
A wide variety of tumor cells exhibit overexpression of urokinase plasminogen activator (uPA) and its receptor (uPAR). In breast cancer, expression of uPA and uPAR is essential for tumor cell invasion and metastasis. It is also known that uPA binds to uPAR and activates the RAS extracellular signal regulated kinase (ERK) signaling pathway. In our study, small interfering RNA (siRNA) was introduced to downregulate the expression of uPA and uPAR in two breast cancer cell lines (MDA MB 231 and ZR 75 1). uPA and uPAR were downregulated individually using single constructs, and in combination using a bicistronic construct driven by a CMV promoter in a pcDNA-3 mammalian expression vector. Reverse transcription PCR (RT-PCR) and Western blot analyses indicated downregulation at both the mRNA and protein levels. In vitro angiogenesis studies using conditioned medium in HMEC-1 cells indicated a decrease in the angiogenic potential of conditioned media from treated cells when compared to the controls. This decrease in angiogenic potential was remarkably higher with the bicistronic construct. Similarly, the invasive potential of these cells decreased dramatically when treated with the bicistronic construct, thereby suggesting a synergistic effect from the downregulation of both uPA and uPAR. Furthermore, when uPA and uPAR were downregulated simultaneously, the apoptotic cascade was triggered as indicated by the upregulation of both initiator and effector caspases as well as other pro-apoptotic molecules. A mitochondrial permeability assay and FACS analysis revealed an increase in apoptotic cells in the uPA/uPAR treatment as compared to the other treatments. This overexpression of pro-apoptotic caspases in relation to the RNAi-induced downregulation of uPA and uPAR clearly suggests the involvement of the uPA-uPAR system in cell survival and proliferation in addition to their role in tumor progression.
Indexed as
Identifiers
16525631PMC1398074W2073485723What OpenQuestion holds
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.