Department of Chemistry and Biology, University of Salerno, Fisciano, 84084 Salerno, Italy.
Department of Translational Medical Sciences, "Federico II" University, 80135 Naples, Italy.
Int J Mol Sci. 2021 Apr 16;22(8):4111. doi: 10.3390/ijms22084111.
Proteolysis is a key event in several biological processes; proteolysis must be tightly controlled because its improper activation leads to dramatic consequences. Deregulation of proteolytic activity characterizes many pathological conditions, including cancer. The plasminogen activation (PA) system plays a key role in cancer; it includes the serine-protease urokinase-type plasminogen activator (uPA). uPA binds to a specific cellular receptor (uPAR), which concentrates proteolytic activity at the cell surface, thus supporting cell migration. However, a large body of evidence clearly showed uPAR involvement in the biology of cancer cell independently of the proteolytic activity of its ligand. In this review we will first describe this multifunctional molecule and then we will discuss how uPAR can sustain most of cancer hallmarks, which represent the biological capabilities acquired during the multistep cancer development. Finally, we will illustrate the main data available in the literature on uPAR as a cancer biomarker and a molecular target in anti-cancer therapy.
蛋白水解作用是几个生物过程中的一个关键事件；蛋白水解作用必须被严格控制，因为其不当的激活会导致严重的后果。蛋白水解活性的失调特征存在于许多病理状况中，包括癌症。纤溶酶原激活（PA）系统在癌症中起着关键作用；它包括丝氨酸蛋白酶尿激酶型纤溶酶原激活剂（uPA）。uPA 与特定的细胞受体（uPAR）结合，将蛋白水解活性集中在细胞表面，从而支持细胞迁移。然而，大量证据清楚地表明 uPAR 参与了癌症细胞的生物学，而与其配体的蛋白水解活性无关。在这篇综述中，我们将首先描述这个多功能分子，然后我们将讨论 uPAR 如何维持大多数癌症的特征，这些特征代表了在癌症多步发展过程中获得的生物学能力。最后，我们将说明文献中关于 uPAR 作为癌症生物标志物和抗癌治疗的分子靶标的主要数据。
Zotero 插件