Department of Pharmacology, School of Pharmaceutical Sciences, Shandong University, 44, West Wenhua Road, Jinan, Shandong Province 250012, China.
Biomed Pharmacother. 2013 Mar;67(2):179-82. doi: 10.1016/j.biopha.2012.10.003. Epub 2012 Nov 15.
The urokinase plasminogen activator system, which is a serine protease family include urokinase-type plasminogen activator (uPA), the uPA receptor and plasminogen activator inhibitors (PAIs). uPA catalyzes the transformation of plasminogen to its active form plasmin, which is able to degrade the extracellular matrix (ECM) and basement membranes, directly or indirectly through activating pro-matrix metalloproteinases (pro-MMPs), promoting cancer cell metastasis and invasion. Both uPA and PAI-1 are poor prognosis markers in primary breast cancer. Evidence has been presented that the uPA system facilitates breast cancer metastasis by several different mechanisms, such as the Ras-ERK pathway and p38 MAPK pathway. This review focuses on uPA system, summarizes their biological effects, highlights the molecular mechanism and pathway, and discusses the role of uPA system in the prevention and treatment of human breast cancers.
尿激酶型纤溶酶原激活系统属于丝氨酸蛋白酶家族，包括尿激酶型纤溶酶原激活物（uPA）、uPA 受体和纤溶酶原激活物抑制剂（PAIs）。uPA 可催化纤溶酶原转化为其活性形式纤溶酶，纤溶酶可直接或间接通过激活前基质金属蛋白酶（pro-MMPs）来降解细胞外基质（ECM）和基底膜，促进癌细胞转移和侵袭。uPA 和 PAI-1 均是原发性乳腺癌预后不良的标志物。有证据表明，尿激酶系统通过多种不同机制促进乳腺癌转移，如 Ras-ERK 途径和 p38 MAPK 途径。本综述重点介绍尿激酶系统，总结其生物学效应，强调分子机制和途径，并讨论尿激酶系统在预防和治疗人类乳腺癌中的作用。
