ArticleNeoplasia (New York, N.Y.)2010
Proprotein convertase inhibition results in decreased skin cell proliferation, tumorigenesis, and metastasis.
Article in Neoplasia (New York, N.Y.), 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers, 1 of them a synthesis that pooled it.
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.
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
28 citing papers in PubMed, 1 synthesis or guideline pooled it, 43 citations in OpenAlex.
- The Biological Activities and Therapeutic Potentials of Baicalein Extracted fromMolecules (Basel, Switzerland) · 2020Pooled it
- The Biology and Clinical Implications of PCSK7.Endocrine reviews · 2025Review
- Identification of Genes Associated with Liver Metastasis in Pancreatic Cancer Reveals PCSK6 as a Crucial Mediator.Cancers · 2022Article
- Inactivation ofCancer research communications · 2022Article
- The Role of Proprotein Convertases in the Regulation of the Function of Immune Cells in the Oncoimmune Response.Frontiers in immunology · 2021Review
- Paired Basic Amino Acid-cleaving Enzyme 4 (PCSK6): An Emerging New Target Molecule in Human Melanoma.Acta dermato-venereologica · 2020Article
- FURIN Inhibition Reduces Vascular Remodeling and Atherosclerotic Lesion Progression in Mice.Arteriosclerosis, thrombosis, and vascular biology · 2019Article
- Development of Novel DNA-Encoded PCSK9 Monoclonal Antibodies as Lipid-Lowering Therapeutics.Molecular therapy : the journal of the American Society of Gene Therapy · 2019Article
- Proprotein convertase subtilisin/kexin type 6 activates the extracellular signal-regulated kinase 1/2 and Wnt family member 3A pathways and promotesOncology letters · 2018Article
- Proprotein convertase inhibition: Paralyzing the cell's master switches.Biochemical pharmacology · 2017Review
- Targeting proprotein convertases in furin-rich lung cancer cells results in decreased in vitro and in vivo growth.Molecular carcinogenesis · 2017Article
- Enhanced aggressiveness of benzopyrene-induced squamous carcinomas in transgenic mice overexpressing the proprotein convertase PACE4 (PCSK6).Molecular carcinogenesis · 2015Article
- Mechanism of Fine-tuning pH Sensors in Proprotein Convertases: IDENTIFICATION OF A pH-SENSING HISTIDINE PAIR IN THE PROPEPTIDE OF PROPROTEIN CONVERTASE 1/3.The Journal of biological chemistry · 2015Article
- Identification of potent and compartment-selective small molecule furin inhibitors using cell-based assays.Biochemical pharmacology · 2015Article
- Expression of paired basic amino acid-cleaving enzyme 4 (PACE4) correlated with prognosis in non-small cell lung cancer (NSCLC) patients.Journal of thoracic disease · 2015Article
- Multi-Leu PACE4 Inhibitor Retention within Cells Is PACE4 Dependent and a Prerequisite for Antiproliferative Activity.BioMed research international · 2015Article
- Proteomic Study to Survey the CIGB-552 Antitumor Effect.BioMed research international · 2015Article
- Enhanced UV-induced skin carcinogenesis in transgenic mice overexpressing proprotein convertases.Neoplasia (New York, N.Y.) · 2013Article
- Overcoming intratumor heterogeneity of polygenic cancer drug resistance with improved biomarker integration.Neoplasia (New York, N.Y.) · 2012Article
- Opposite roles of furin and PC5A in N-cadherin processing.Neoplasia (New York, N.Y.) · 2012Article
Corrections and comments
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
Abstract
PACE4 is a proprotein convertase (PC) responsible for cleaving and activating proteins that contribute to enhance tumor progression. PACE4 overexpression significantly increased the susceptibility to carcinogenesis, leading to enhanced tumor cell proliferation and premature degradation of the basement membrane. In the present study, we sought to evaluate a novel approach to retard skin tumor progression based on the inhibition of PACE4. We used decanoyl-RVKR-chloromethylketone (CMK), a small-molecule PC inhibitor, for in vitro and in vivo experiments. We found that CMK-dependent blockage of PACE4 activity in skin squamous cell carcinoma cell lines resulted in impaired insulin-like growth factor 1 receptor maturation, diminished its intrinsic tyrosine kinase activity, and decreased tumor cell proliferation. Two-stage skin chemical carcinogenesis experiments, together with topical applications of CMK, demonstrated that this PC inhibitor markedly reduced tumor incidence, tumor multiplicity, and metastasis, pointing to a significant delay in tumor progression in wild-type and PACE4 transgenic mice. These results identify PACE4, together with other PCs, as suitable targets to slow down or block tumor progression, suggesting that PC inhibition is a potential approach for therapy for solid tumors.
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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.