Iftikhar Ali, Mahmood Niaz, Rabbani Shafaat A
Department of Human Genetics, McGill University, Montréal, QC H4A 3J1, Canada.
Department of Medicine, McGill University, Montréal, QC H4A 3J1, Canada.
Cancers (Basel). 2025 Oct 14;17(20):3309. doi: 10.3390/cancers17203309.
The urokinase-type plasminogen activator receptor (uPAR) plays a pivotal role in regulating extracellular proteolysis, cell migration, immune responses, and tissue remodeling across diverse physiological and pathological contexts. This review provides detailed insights into the structure of uPAR, ligand interactions, and signaling mechanisms, emphasizing its central function in cancer progression, including tumor invasion, metastasis, angiogenesis, and modulation of the tumor microenvironment. We also summarize the involvement of uPAR as a key player in cardiovascular, infectious, and neurological diseases, where it contributes to inflammation, tissue damage, and disease progression. However, translational gaps remain, most notably inconsistent assay harmonization (especially for suPAR), uncertain context-specific cut-offs and patient-selection criteria and limited multicenter validation for uPAR-targeted imaging and therapeutics. This review addresses these gaps by synthesizing cross-disease evidence to clarify clinical use cases and outline practical selection frameworks. Furthermore, we discuss the clinical potential of uPAR as a diagnostic and prognostic biomarker in diverse disease contexts, along with recent advances in therapeutic strategies targeting uPAR.
尿激酶型纤溶酶原激活物受体（uPAR）在各种生理和病理情况下调节细胞外蛋白水解、细胞迁移、免疫反应和组织重塑中起着关键作用。本综述详细介绍了uPAR的结构、配体相互作用和信号传导机制，强调了其在癌症进展中的核心作用，包括肿瘤侵袭、转移、血管生成和肿瘤微环境的调节。我们还总结了uPAR作为心血管、感染性和神经疾病中的关键参与者的作用，它在这些疾病中导致炎症、组织损伤和疾病进展。然而，转化差距仍然存在，最明显的是检测方法不一致（特别是对于可溶性uPAR）、特定背景下的临界值和患者选择标准不确定，以及针对uPAR的成像和治疗方法的多中心验证有限。本综述通过综合跨疾病证据来填补这些差距，以阐明临床应用案例并概述实用的选择框架。此外，我们还讨论了uPAR作为不同疾病背景下的诊断和预后生物标志物的临床潜力，以及针对uPAR的治疗策略的最新进展。
