Smith Harvey W, Marra Pierfrancesco, Marshall Christopher J
Cancer Research UK Centre for Cell and Molecular Biology, Institute of Cancer Research, London, England, UK.
J Cell Biol. 2008 Aug 25;182(4):777-90. doi: 10.1083/jcb.200712050.
The urokinase-type plasminogen activator receptor (uPAR) drives tumor cell membrane protrusion and motility through activation of Rac; however, the pathway leading from uPAR to Rac activation has not been described. In this study we identify DOCK180 as the guanine nucleotide exchange factor acting downstream of uPAR. We show that uPAR cooperates with integrin complexes containing beta(3) integrin to drive formation of the p130Cas-CrkII signaling complex and activation of Rac, resulting in a Rac-driven elongated-mesenchymal morphology, cell motility, and invasion. Our findings identify a signaling pathway underlying the morphological changes and increased cell motility associated with uPAR expression.
尿激酶型纤溶酶原激活物受体（uPAR）通过激活Rac驱动肿瘤细胞膜突出和运动；然而，从uPAR到Rac激活的信号通路尚未被描述。在本研究中，我们确定DOCK180为在uPAR下游起作用的鸟嘌呤核苷酸交换因子。我们发现uPAR与含有β3整合素的整合素复合物协同作用，驱动p130Cas-CrkII信号复合物的形成和Rac的激活，导致Rac驱动的细长间充质形态、细胞运动和侵袭。我们的研究结果确定了一条与uPAR表达相关的形态变化和细胞运动增加的信号通路。
