The Urokinase System in Cancer: From Stress Responses to Therapeutic Targeting

A special issue of Biomolecules (ISSN 2218-273X).

Deadline for manuscript submissions: 3 April 2026 | Viewed by 1413

Special Issue Editors


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Guest Editor
Department of Biology, Division of Molecular Biology, Faculty of Science, University of Zagreb, Horvatovac 102, 10000 Zagreb, Croatia
Interests: tumor cell; urokinase plasminogen activator; cell signaling
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Special Issue Information

Dear Colleagues,

Today, ischemic cerebral vascular events are one of the main causes of morbidity, with plasminogen activators being widely used as thrombolytic agents in clinics in different cases of blood vessels’ blood clot occlusions. However, the plasminogen activation system also has numerous other physiological and pathological functions, such as tissue remodeling and wound healing, cell migration and invasion, tumor metastases, etc. Although plasminogen is ubiquitous, the production of plasmin is closely controlled by the plasminogen activation system, consisting of tissue (tPA) and urokinase plasminogen activators (uPAs), its inhibitors and uPAR, a membrane urokinase receptor. Plasminogen activation system molecules are regulated at the level of transcription. They are also finely tuned and responsive to different cues, such as hormones, growth factors, chemotherapeutic agents, and DNA damage. Mechanisms of their regulation—not only on the level of transcription but also on the level of translation—secretion, and interactions with other molecules are still not known well enough. uPA, PAI1 and uPAR can influence cell proliferation, activate different signaling pathways in a cell-specific way, and regulate cell migration and invasion of tumor cells. This Special Issue will cover topics encompassing the mechanisms of urokinase plasminogen activation system molecules’ regulation in tumor cells and their use in diagnostics, prognostics and targeted therapy.

Potential topics of interest include, but are not limited to, the following:

  • Mechanisms of urokinase, PAI1 and uPAR promoter regulation;
  • Regulation of uPA, PAI1 and uPAR expression and secretion;
  • Molecular interactions of uPAR, PAI1 and uPA and their roles in cell migration, cell invasion and interactions with the microenvironment;
  • Regulation of physiological and pathological processes via the plasminogen activation system in different tissues and organs;
  • Prognostic and diagnostic roles of urokinase, PAI1 and uPAR;
  • Therapeutic targeting of plasminogen activator system molecules.

Dr. Maja Matulić
Dr. Petra Korać
Guest Editors

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Keywords

  • urokinase plasminogen activator
  • PAI1
  • urokinase plasminogen activator receptor
  • transcription
  • regulation
  • cancer
  • migration
  • invasion
  • stress

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Published Papers (1 paper)

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Review

15 pages, 1569 KB  
Review
Plasminogen Activator Inhibitor-1 in Skin Malignancies: Therapeutic Implications of Its Inhibition
by Taku Fujimura, Yusuke Muto and Yoshihide Asano
Biomolecules 2025, 15(9), 1317; https://doi.org/10.3390/biom15091317 - 13 Sep 2025
Viewed by 1186
Abstract
Plasminogen activator inhibitor-1 (PAI-1), a key regulator of fibrinolysis, has emerged as a critical stromal factor that contributes to tumor progression in various malignancies, including skin cancers. Beyond its classical role in inhibiting plasminogen activators, PAI-1 exerts pleiotropic effects within the tumor microenvironment, [...] Read more.
Plasminogen activator inhibitor-1 (PAI-1), a key regulator of fibrinolysis, has emerged as a critical stromal factor that contributes to tumor progression in various malignancies, including skin cancers. Beyond its classical role in inhibiting plasminogen activators, PAI-1 exerts pleiotropic effects within the tumor microenvironment, promoting immunosuppression, angiogenesis, and extracellular matrix remodeling. This review highlights the tumor-promoting functions of PAI-1 in melanoma, cutaneous squamous cell carcinoma, cutaneous angiosarcoma and cutaneous T-cell lymphoma, with a particular focus on its modulation of tumor-associated macrophages, cancer-associated fibroblasts, and endothelial cells. We also discuss recent preclinical and clinical studies targeting PAI-1, including TM5614, a novel oral PAI-1 inhibitor currently under investigation in phase II /III trials. By summarizing the multifaceted roles of PAI-1 and its impact on the immune and stromal landscape of skin malignancies, this review provides a rationale for PAI-1 as a promising therapeutic target and calls for further clinical validation of PAI-1–directed therapies. Full article
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