Wang Y
Orthopaedic Research Institute, St George Hospital, University of New South Wales, Sydney, NSW 2145, Australia.
Med Res Rev. 2001 Mar;21(2):146-70. doi: 10.1002/1098-1128(200103)21:2<146::aid-med1004>3.0.co;2-b.
This article reviews the role of urokinase-type plasminogen activator receptor (uPAR) and its protein, mRNA, cDNA, genomic organization, promoter, transcription activation factors, and signal transduction. The uPAR has been implicated in several biological processes including angiogenesis, monocyte migration, cancer metastasis, trophoblast implantation, and wound healing. It is a specific cell surface receptor for its ligand uPA which catalyzes the formation of plasmin from plasminogen to generate the proteolytic cascade that contributes to the breakdown of extracellular matrix, a key step in cancer metastasis. The uPAR is a 55-60 kDa glycoprotein organized as three homologous cysteine-rich domains. It attaches to the plasma membrane via a covalent linkage to a glycosyl-phosphatidylinositol (GPI) moiety and appears to play an important role in transmembrane signalling. The 1.4-kb human uPAR cDNA and 21.23-kb genomic DNA have been cloned and the gene contains seven exons. The uPAR promoter region was defined in a 188 bp fragment between bases -141 and +47 relative to the transcription start site. Binding of transcription factors (Sp1, AP-2, NFkappaB and two AP-1) to the uPAR promoter region activates the basal transcription of the gene. There is a strong correlation between uPAR expression and the invasive cancer cell phenotype. uPAR may play a critical role in the process of cancer invasion and metastasis, as antisense uPAR mRNA can inhibit cancer spread in vitro and in vivo. These studies may provide a novel therapeutic target for blocking cancer invasion and metastasis.
本文综述了尿激酶型纤溶酶原激活物受体（uPAR）及其蛋白、mRNA、cDNA、基因组结构、启动子、转录激活因子和信号转导的作用。uPAR参与了包括血管生成、单核细胞迁移、癌症转移、滋养层植入和伤口愈合在内的多种生物学过程。它是其配体uPA的特异性细胞表面受体，uPA催化纤溶酶原形成纤溶酶，从而产生蛋白水解级联反应，这是癌症转移的关键步骤，有助于细胞外基质的分解。uPAR是一种55 - 60 kDa的糖蛋白，由三个富含半胱氨酸的同源结构域组成。它通过与糖基磷脂酰肌醇（GPI）部分的共价连接附着于质膜，似乎在跨膜信号传导中起重要作用。1.4 kb的人uPAR cDNA和21.23 kb的基因组DNA已被克隆，该基因包含七个外显子。uPAR启动子区域在相对于转录起始位点的 - 141至 + 47碱基之间的188 bp片段中被确定。转录因子（Sp1、AP - 2、NFκB和两个AP - 1）与uPAR启动子区域的结合激活了该基因的基础转录。uPAR表达与侵袭性癌细胞表型之间存在很强的相关性。uPAR可能在癌症侵袭和转移过程中起关键作用，因为反义uPAR mRNA可以在体外和体内抑制癌症扩散。这些研究可能为阻断癌症侵袭和转移提供一个新的治疗靶点。
