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
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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“For example, the plasminogen system has been linked to cancer with expression of PAI-1 linked to poor outcome in breast cancer (70).”
From Diabetes and Cancer (2010) · cites this paper as [70]
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7 retracted
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
RetractedKong, 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
RetractedGondi, 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
RetractedKunigal, 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
RetractedPulukuri, 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
RetractedPulukuri, S. M. K., & Rao, J. S. (2007) · Cancer Research · doi:10.1158/0008-5472.can-07-0751 · Cited by 62
RetractedPulukuri, S. M. K., Gorantla, B., & Rao, J. S. (2007) · Journal of Biological Chemistry · doi:10.1074/jbc.m705867200 · Cited by 51
RetractedHanahan, D., & Weinberg, R. A. (2000) · Cell · doi:10.1016/s0092-8674(00)81683-9 · Cited by 29,219
Tumor angiogenesis: therapeutic implications
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Diabetes and Cancer: A Consensus Report
Giovannucci, E. L., Harlan, D. M., Archer, M. C., Bergenstal, R. M., Gapstur, S. M., Habel, L. A., Pollak, M., Regensteiner, J. G., & Yee, D. (2010) · CA A Cancer Journal for Clinicians · doi:10.3322/caac.20078 · Cited by 1,082
Remarkable Potential of the α-Aminophosphonate/Phosphinate Structural Motif in Medicinal Chemistry
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Exploring the next generation of antibody–drug conjugates
Tsuchikama, K., Anami, Y., Ha, S. Y. Y., & Yamazaki, C. M. (2024) · Nature Reviews Clinical Oncology · doi:10.1038/s41571-023-00850-2 · Cited by 659
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Metadata
- Authors
- Ulisse, S., Baldini, E., Sorrenti, S., & D'Armiento, M.
- Affiliations
- Sapienza University of Rome (IT)
- 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)
- 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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