A suppressor of multiple extracellular matrix-degrading proteases and cancer metastasis.
A suppressor of multiple extracellular matrix-degrading proteases and cancer metastasis.
复制标题
多种细胞外基质降解蛋白酶和癌症转移的抑制剂
DOI：
10.1111/j.1582-4934.2008.00576.x
复制
发表时间：
2009-09
影响因子：
5.3
通讯作者：
Chan HC
中科院分区：
文献类型：
--
作者：
Yin LL;Chung CM;Chen J;Fok KL;Ng CP;Jia RR;Ren X;Zhou J;Zhang T;Zhao XH;Lin M;Zhu H;Zhang XH;Tsang LL;Bi Y;Zhou Z;Mo F;Wong N;Chung YW;Sha J;Chan HC
癌症转移仍然是癌症生物学中了解最少的过程。它涉及细胞外基质（ECM）蛋白的降解由一系列的“肿瘤相关”蛋白酶。在这里，我们报告了一个新的蛋白酶抑制剂，NYD-SP 8，这是位于人类染色体19q13.2的鉴定。NYD-SP 8编码一个27 kD的GPI锚定的细胞表面蛋白，其显示与尿激酶纤溶酶原激活物受体（uPAR）的结构同源性。免疫共沉淀实验表明NYD-SP 8与uPA/uPAR复合物结合并干扰uPA的活性产生。NYD-SP 8的过表达导致已知参与ECM降解的三种主要类型的蛋白酶（包括uPA、基质金属蛋白酶（MMP）和组织蛋白酶B）的活性降低，导致体外和体内癌细胞侵袭和转移的抑制。这些数据表明NYD-SP 8在调节ECM降解中的重要作用，提供了在抑制癌症进展中调节尿激酶信号传导的新机制。
Cancer metastasis remains the most poorly understood process in cancer biology. It involves the degradation of extracellular matrix (ECM) proteins by a series of ‘tumour-associated’ proteases. Here we report the identification of a novel protease suppressor, NYD-SP8, which is located on human chromosome 19q13.2. NYD-SP8 encodes a 27 kD GPI-anchored cell surface protein, which shows structural homology to urokinase plasminogen activator receptor (uPAR). Co-immunoprecipitation experiments showed that NYD-SP8 binds to uPA/uPAR complexes and interfere with active uPA production. Overexpression of NYD-SP8 results in reducing activities of the three major classes of proteases known to be involved in ECM degradation, including uPA, matrix metalloproteinases (MMPs) and cathepsin B, leading to suppression of both in vitro and in vivo cancer cell invasion and metastasis. These data demonstrate an important role of NYD-SP8 in regulating ECM degradation, providing a novel mechanism that modulates urokinase signalling in the suppression of cancer progression.