ArticlePloS one2010
Downregulation of uPAR and cathepsin B induces apoptosis via regulation of Bcl-2 and Bax and inhibition of the PI3K/Akt pathway in gliomas.
Article in PloS one, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It has been retracted, and should not be counted. Cited by 43 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
43 citing papers in PubMed, 93 citations in OpenAlex.
- A Phase Ib/II, open-label, multicenter study of INC280 (capmatinib) alone and in combination with buparlisib (BKM120) in adult patients with recurrent glioblastoma.Journal of neuro-oncology · 2020Trial
- Development of Cathepsin B‑Activatable Cell-Penetrating Peptides for Tumor Targeting.ACS pharmacology & translational science · 2026Article
- DNA methylation of theiScience · 2026Article
- Pluronic-F-127-Passivated SnOPlants (Basel, Switzerland) · 2023Article
- Human antibody VFrontiers in oncology · 2023Article
- Lysosomal peptidases-intriguing roles in cancer progression and neurodegeneration.FEBS open bio · 2022Review
- Modulation of Cellular Function by the Urokinase Receptor Signalling: A Mechanistic View.Frontiers in cell and developmental biology · 2022Review
- Preliminary study of Yinhuapinggan granule against H1N1 influenza virus infection in mice through inhibition of apoptosis.Pharmaceutical biology · 2020Article
- Inhibition of Glioma Cell Growth and Apoptosis Induction through Targeting Wnt10B Expression by Pyrazolo[4,3-c]pyridine-4-one.Medical science monitor : international medical journal of experimental and clinical research · 2020Article
- Recent Advances on Drug-Loaded Mesenchymal Stem Cells With Anti-neoplastic Agents for Targeted Treatment of Cancer.Frontiers in bioengineering and biotechnology · 2020Review
- Article
- Human amniotic mesenchymal stem cells and their paracrine factors promote wound healing by inhibiting heat stress-induced skin cell apoptosis and enhancing their proliferation through activating PI3K/AKT signaling pathway.Stem cell research & therapy · 2019Article
- Prognostic and therapeutic relevance of cathepsin B in pediatric acute myeloid leukemia.American journal of cancer research · 2019Article
- MicroRNA-383 upregulation protects against propofol-induced hippocampal neuron apoptosis and cognitive impairment.Experimental and therapeutic medicine · 2018Article
- [Inhibitory Eefects of the novel tyrosine kinase inhibitor BGJ398 against human leukemic cell line KG-1 cells].Zhonghua xue ye xue za zhi = Zhonghua xueyexue zazhi · 2018Article
- uPAR promotes tumor-like biologic behaviors of fibroblast-like synoviocytes through PI3K/Akt signaling pathway in patients with rheumatoid arthritis.Cellular & molecular immunology · 2018Article
- CREB1 regulates glucose transport of glioma cell line U87 by targeting GLUT1.Molecular and cellular biochemistry · 2017Article
- Neuron specific enolase is a potential target for regulating neuronal cell survival and death: implications in neurodegeneration and regeneration.Neuroimmunology and neuroinflammation · 2017Article
- Lipid Raft Integrity Is Required for Survival of Triple Negative Breast Cancer Cells.Journal of breast cancer · 2016Article
- CSTB Downregulation Promotes Cell Proliferation and Migration and Suppresses Apoptosis in Gastric Cancer SGC-7901 Cell Line.Oncology research · 2016Article
Corrections and comments
- Retraction · 2020-01-29Duplication of/in Image · Falsification/Fabrication of Data · Investigation by Company/Institution · Misconduct - Official Investigation(s) and/or Finding(s) · Misconduct by Author · · Jasti S Rao has institutional finding of misconduct
- Retracted
Authors and funding
8 authors at 2 institutions in 1 country.
Funding
Abstract
backgroundGlioma is the most commonly diagnosed primary brain tumor and is characterized by invasive and infiltrative behavior. uPAR and cathepsin B are known to be overexpressed in high-grade gliomas and are strongly correlated with invasive cancer phenotypes. METHODOLOGY/PRINCIPAL
findingsIn the present study, we observed that simultaneous downregulation of uPAR and cathepsin B induces upregulation of some pro-apoptotic genes and suppression of anti-apoptotic genes in human glioma cells. uPAR and cathepsin B (pCU)-downregulated cells exhibited decreases in the Bcl-2/Bax ratio and initiated the collapse of mitochondrial membrane potential. We also observed that the broad caspase inhibitor, Z-Asp-2, 6-dichlorobenzoylmethylketone rescued pCU-induced apoptosis in U251 cells but not in 5310 cells. Immunoblot analysis of caspase-9 immunoprecipitates for Apaf-1 showed that uPAR and cathepsin B knockdown activated apoptosome complex formation in U251 cells. Downregulation of uPAR and cathepsin B also retarded nuclear translocation and interfered with DNA binding activity of CREB in both U251 and 5310 cells. Further western blotting analysis demonstrated that downregulation of uPAR and cathepsin B significantly decreased expression of the signaling molecules p-PDGFR-β, p-PI3K and p-Akt. An increase in the number of TUNEL-positive cells, increased Bax expression, and decreased Bcl-2 expression in nude mice brain tumor sections and brain tissue lysates confirm our in vitro results. CONCLUSIONS/SIGNIFICANCE: In conclusion, RNAi-mediated downregulation of uPAR and cathepsin B initiates caspase-dependent mitochondrial apoptosis in U251 cells and caspase-independent mitochondrial apoptosis in 5310 cells. Thus, targeting uPAR and cathepsin B-mediated signaling using siRNA may serve as a novel therapeutic strategy for the treatment of gliomas.
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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.