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

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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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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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