Cited by 322Protease and Inhibitor MechanismsBlood Coagulation and Thrombosis MechanismsTGF-β signaling in diseases

The DOI matches its Crossref record; 494 of the 494 references it cites were found in a registry or an index.

The Urokinase Plasminogen Activator System: A Target for Anti-Cancer Therapy

Ulisse, Salvatore, Baldini, Enke, Sorrenti, Salvatore, D'Armiento, Massimino·2009·Current Cancer Drug Targets

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Abstract

The urokinase plasminogen activator (uPA) system (uPAS) consists of the uPA, its cognate receptor (uPAR) and two specific inhibitors, the plasminogen activator inhibitor 1 (PAI-1) and 2 (PAI-2). The uPA converts the proenzyme plasminogen in the serine protease plasmin, involved in a number of physiopathological processes requiring basement membrane (BM) and/or extracellular matrix (ECM) remodelling, including tumor progression and metastasis. Data accumulated over the past years have made increasingly clear that the uPAS has a multifunctional task in the neoplastic evolution, affecting tumor angiogenesis, malignant cell proliferation, adhesion and migration, intravasation and growth at the metastatic site. In agreement with their role in cancer progression and metastasis, an increased expression of uPA, uPAR, and PAI-1 has been documented in several malignant tumors, and a positive correlation between the levels of one or more uPAS members and a poor prognosis has been frequently reported. This is particularly evident in breast cancer, for which uPA has been demonstrated to be the most potent independent prognostic factor described to date. The involvement of the uPAS in cancer progression identifies its components as suitable targets for anti-cancer therapy. Several therapeutical approaches aimed at inhibiting the uPA/uPAR functions have been shown to possess anti-tumor effects in xenograft models, including selective inhibitors of uPA activity, antagonist peptides, monoclonal antibodies able to prevent uPA binding to uPAR and gene therapy techniques silencing uPA/uPAR expression. All these strategies, however, although promising, need definitive confirmation in humans as, up to now, only few uPA inhibitors entered clinical trial.

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RNA Interference-directed Knockdown of Urokinase Plasminogen Activator and Urokinase Plasminogen Activator Receptor Inhibits Prostate Cancer Cell Invasion, Survival, and Tumorigenicity in Vivo
Pulukuri, S. M. K., Gondi, C. S., Lakka, S. S., Jutla, A., Estes, N. C., Gujrati, M., & Rao, J. S. (2005) · Journal of Biological Chemistry · doi:10.1074/jbc.m503111200 · Cited by 283
Retracted
Inhibition of Angiogenesis and Invasion by 3,3′-Diindolylmethane Is Mediated by the Nuclear Factor–κB Downstream Target Genes MMP-9 and uPA that Regulated Bioavailability of Vascular Endothelial Growth Factor in Prostate Cancer
Kong, D., Li, Y., Wang, Z. P., Banerjee, S., & Sarkar, F. H. (2007) · Cancer Research · doi:10.1158/0008-5472.can-06-4277 · Cited by 196
Retracted
RETRACTED ARTICLE: RNAi-mediated inhibition of cathepsin B and uPAR leads to decreased cell invasion, angiogenesis and tumor growth in gliomas
Gondi, C. S., Lakka, S. S., Dinh, D. H., Olivero, W. C., Gujrati, M., & Rao, J. S. (2004) · Oncogene · doi:10.1038/sj.onc.1207879 · Cited by 141
Retracted
Retracted: RNAi‐mediated downregulation of urokinase plasminogen activator receptor and matrix metalloprotease‐9 in human breast cancer cells results in decreased tumor invasion, angiogenesis and growth
Kunigal, S., Lakka, S. S., Gondi, C. S., Estes, N. C., & Rao, J. S. (2007) · International Journal of Cancer · doi:10.1002/ijc.22962 · Cited by 85
Retracted
Demethylation-Linked Activation of Urokinase Plasminogen Activator Is Involved in Progression of Prostate Cancer
Pulukuri, S. M. K., Estes, N. C., Patel, J. C., & Rao, J. S. (2007) · Cancer Research · doi:10.1158/0008-5472.can-06-2892 · Cited by 85
Retracted
Small Interfering RNA–Directed Reversal of Urokinase Plasminogen Activator Demethylation Inhibits Prostate Tumor Growth and Metastasis
Pulukuri, S. M. K., & Rao, J. S. (2007) · Cancer Research · doi:10.1158/0008-5472.can-07-0751 · Cited by 62
Retracted
Inhibition of Histone Deacetylase Activity Promotes Invasion of Human Cancer Cells through Activation of Urokinase Plasminogen Activator
Pulukuri, S. M. K., Gorantla, B., & Rao, J. S. (2007) · Journal of Biological Chemistry · doi:10.1074/jbc.m705867200 · Cited by 51
Retracted
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“Although impairment of uPAR function or inhibition of its expression was associated with impaired invasive, metastatic, and tumorigenic potential of many tumor models in vitro and in vivo [4,11,12,14,16,17,20,52,57,79,84,85], one study in transgenic mice with uPAR gene ablation showed no pronounced causal effects on d…”
BackgroundInfluential
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Authors: Ulisse, S., Baldini, E., Sorrenti, S., & D'Armiento, M.
Affiliations: Sapienza University of Rome (IT)
ORCID: Ulisse, Salvatore
Baldini, Enke
Sorrenti, Salvatore
Venue: Current Cancer Drug Targets
Publisher: Bentham Science Publishers Ltd.
Published: 2009-02-01
Volume: 9
Issue: 1
Pages: 32-71
ISSN: 1568-0096 (ISSN-L)
DOI: 10.2174/156800909787314002
OpenAlex: W2135351121
Cited by: 312
References: 493
Citations by year: 2026: 6 · 2025: 6 · 2024: 8 · 2023: 8 · 2022: 16 · 2021: 18 · 2020: 14 · 2019: 16 · 2018: 16 · 2017: 17 · 2016: 17 · 2015: 23 · 2014: 33 · 2013: 31 · 2012: 25
FWCI: 9.37
Type: journal article
Language: en
Open access: closed
Locations: Current Cancer Drug Targets (publishedVersion)
PubMed (publishedVersion)
IRIS Research product catalog (Sapienza University of Rome) (submittedVersion)
Topics: Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Protease and Inhibitor Mechanisms
Health Sciences › Medicine › Hematology › Blood Coagulation and Thrombosis Mechanisms
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › TGF-β signaling in diseases
Keywords: urokinase, urokinase receptor, plasminogen activator inhibitor-1, plasminogen activator inhibitor-2, plasmin, extracellular matrix remodeling, metastasis, tumor progression, tumor angiogenesis, breast cancer, prognostic factors, cancer therapy, uPA inhibitors, monoclonal antibodies, gene therapy, xenograft models
MeSH terms: Antineoplastic Agents, Humans, Neoplasms, Urokinase-Type Plasminogen Activator

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The Urokinase Plasminogen Activator System: A Target for Anti-Cancer Therapy

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