Multifaceted Role of the Urokinase-Type Plasminogen Activator (uPA) and Its Receptor (uPAR): Diagnostic, Prognostic, and Therapeutic Applications.
Multifaceted Role of the Urokinase-Type Plasminogen Activator (uPA) and Its Receptor (uPAR): Diagnostic, Prognostic, and Therapeutic Applications.
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DOI：
10.3389/fonc.2018.00024
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发表时间：
2018
影响因子：
4.7
通讯作者：
Rabbani SA
中科院分区：
文献类型：
--
作者：
Mahmood N;Mihalcioiu C;Rabbani SA
纤溶酶原激活剂（PA）系统是与各种生理和病理生理过程相关的细胞外蛋白水解酶系统。大量证据表明，PA系统的各个组成部分中，尿激酶型纤溶酶原激活剂（uPA）、其受体（uPAR）以及纤溶酶原激活剂抑制剂-1和-2（PAI-1和PAI-2）在肿瘤进展和转移中发挥着重要作用。 uPA 与 uPAR 的结合有助于将纤溶酶原激活为纤溶酶，进而启动一系列蛋白水解级联反应，降解细胞外基质的成分，从而导致肿瘤细胞从原发部位迁移到远处的次要器官。 PA 系统的组成部分在几种常见恶性肿瘤中表现出改变的表达模式，这已将其确定为降低癌症相关发病率和死亡率的理想诊断、预后和治疗靶点。这篇综述总结了 PA 系统的各个组成部分，重点关注 uPA-uPAR 在不同生物过程中的作用，特别是在恶性肿瘤的背景下。我们还讨论了针对各种恶性肿瘤的 uPA-uPAR 靶向诊断和治疗策略的当前知识状况。
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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