ReviewInternational journal of molecular sciences2020
The Role of Extracellular Proteases in Tumor Progression and the Development of Innovative Metal Ion Chelators that Inhibit their Activity.
Review in International journal of molecular sciences, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers, 1 of them a synthesis that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
The trial behind it
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
26 citing papers in PubMed, 1 synthesis or guideline pooled it, 63 citations in OpenAlex.
- The entanglement of extracellular matrix molecules and immune checkpoint inhibitors in cancer: a systematic review of the literature.Frontiers in immunology · 2023Pooled it
- Multi-omics prediction of key proteases regulating scar formation and neural repair after spinal cord injury.Neural regeneration research · 2026Article
- Protease inhibition: breaking the barriers of chemoresistance in cancer.Molecular biology reports · 2026Review
- Article
- Peptides in the Diagnosis and Treatment of Pancreatic Cancer and Other Pancreatic Diseases from Basic Research to Clinical Translation.Drug design, development and therapy · 2026Review
- Increasing the odds: antibody-mediated delivery of two distinct immunogenic T-cell epitopes with one antibody.Oncoimmunology · 2025Article
- ARHGEF6 downregulation as a key mediator of tumor cell apoptosis in breast cancer.Oncology letters · 2025Article
- Atypical contribution of caspase-3 to melanoma cancer cell motility by regulation of coronin 1B activity.Cell death & disease · 2025Article
- PERRC: Protease Engineering with Reactant Residence Time Control.ACS synthetic biology · 2025Article
- Apoptotic Caspases-3 and -7 Cleave Extracellular Domains of Membrane-Bound Proteins from MDA-MB-231 Breast Cancer Cells.International journal of molecular sciences · 2025Article
- Review
- Proteases: Role in Various Human Diseases.Current pharmaceutical biotechnology · 2025Review
- Efficacy and survival outcomes of bevacizumab plus minocycline for glioblastoma.American journal of translational research · 2025Article
- Substrate O-glycosylation actively regulates extracellular proteolysis.Protein science : a publication of the Protein Society · 2024Article
- Glycooligomer-Functionalized Catalytic Nanocompartments Co-Loaded with Enzymes Support Parallel Reactions and Promote Cell Internalization.Biomacromolecules · 2024Article
- Contrast Agents Based on Human Serum Albumin and Nitroxides forInternational journal of molecular sciences · 2024Article
- Hypoxia-driven protease legumain promotes immunosuppression in glioblastoma.Cell reports. Medicine · 2023Article
- Ligand-Gated Ion Channels: Prognostic and Therapeutic Implications for Gliomas.Journal of personalized medicine · 2023Review
- Chemistry towards Biology.International journal of molecular sciences · 2023Article
- Deciphering Mechanisms of Action of Sortilin/Neurotensin Receptor-3 in the Proliferation Regulation of Colorectal and Other Cancers.International journal of molecular sciences · 2022Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
3 authors at 2 institutions in 2 countries.
Funding
Abstract
The crucial role of extracellular proteases in cancer progression is well-known, especially in relation to the promotion of cell invasion through extracellular matrix remodeling. This also occurs by the ability of extracellular proteases to induce the shedding of transmembrane proteins at the plasma membrane surface or within extracellular vesicles. This process results in the regulation of key signaling pathways by the modulation of kinases, e.g., the epidermal growth factor receptor (EGFR). Considering their regulatory roles in cancer, therapeutics targeting various extracellular proteases have been discovered. These include the metal-binding agents di-2-pyridylketone 4,4-dimethyl-3-thiosemicarbazone (Dp44mT) and di-2-pyridylketone-4-cyclohexyl-4-methyl-3-thiosemicarbazone (DpC), which increase c-MET degradation by multiple mechanisms. Both the direct and indirect inhibition of protease expression and activity can be achieved through metal ion depletion. Considering direct mechanisms, chelators can bind zinc(II) that plays a catalytic role in enzyme activity. In terms of indirect mechanisms, Dp44mT and DpC potently suppress the expression of the kallikrein-related peptidase-a prostate-specific antigen-in prostate cancer cells. The mechanism of this activity involves promotion of the degradation of the androgen receptor. Additional suppressive mechanisms of Dp44mT and DpC on matrix metalloproteases (MMPs) relate to their ability to up-regulate the metastasis suppressors N-myc downstream regulated gene-1 (NDRG1) and NDRG2, which down-regulate MMPs that are crucial for cancer cell invasion.
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What 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.