Multifaceted Role of the Urokinase-Type Plasminogen Activator (uPA) and Its Receptor (uPAR): Diagnostic, Prognostic, and Therapeutic Applications
Open accessAbstract
The plasminogen activator (PA) system is an extracellular proteolytic enzyme system associated with various physiological and pathophysiological processes. A large body of evidence support that among the various components of the PA system, urokinase-type plasminogen activator (uPA), its receptor (uPAR), and plasminogen activator inhibitor-1 and -2 (PAI-1 and PAI-2) play a major role in tumor progression and metastasis. The binding of uPA with uPAR is instrumental for the activation of plasminogen to plasmin, which in turn initiates a series of proteolytic cascade to degrade the components of the extracellular matrix, and thereby, cause tumor cell migration from the primary site of origin to a distant secondary organ. The components of the PA system show altered expression patterns in several common malignancies, which have identified them as ideal diagnostic, prognostic, and therapeutic targets to reduce cancer-associated morbidity and mortality. This review summarizes the various components of the PA system and focuses on the role of uPA-uPAR in different biological processes especially in the context of malignancy. We also discuss the current state of knowledge of uPA-uPAR-targeted diagnostic and therapeutic strategies for various malignancies.
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The binding of uPA and its receptor (uPAR) helps activate the serine protease plasminogen to become plasmin, starting a series of proteolytic cascade reactions to break down the extracellular matrix's components and encourage tumor invasion and metastasis.
“The binding of uPA and its receptor (uPAR) will help activate the serine protease plasminogen to become plasmin. Afterwards, start a series of proteolytic cascade reactions to break down the extracellular matrix’s components and encourage tumor invasion and metastasis.142,151”
From Smart nanoparticles for cancer therapy (2023) · cites this paper as [151]
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References 282 · Cited by 478
Research works printed but not linked: 1
- [25]Sobel G Mohler S Jones N Dowdy A Guest M, editors. Urokinase-an activator of plasma profibrinolysin extracted from urine. Am J Physiol (1952) 171(3): 768– 9.
- Authors
- Mahmood, N., Mihalcioiu, C., & Rabbani, S. A.
- Affiliations
- McGill University Health Centre (CA)
- Corresponding author
- Rabbani, Shafaat A.
- Venue
- Frontiers in Oncology
- Publisher
- Frontiers Media SA
- Published
- 2018-02-12
- Volume
- 8
- Pages
- 24-24
- ISSN
- 2234-943X (ISSN-L)
- PMC
- PMC5816037
- OpenAlex
- W2791482536
- Cited by
- 478
- References
- 282
- Citations by year
- 2026: 34 · 2025: 54 · 2024: 56 · 2023: 54 · 2022: 89 · 2021: 90 · 2020: 48 · 2019: 40 · 2018: 13
- FWCI
- 4.96
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- Frontiers in Oncology (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- Canadian Institutes of Health Research (MOP 130410)
- 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, uPAR, plasminogen activation system, plasminogen activation, metastasis, tumor progression, extracellular matrix degradation, tumor cell migration, tumor markers, prognostic factors, targeted cancer therapy, plasminogen activator inhibitor-1, plasminogen activator inhibitor-2
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