EGFR is a transducer of the urokinase receptor initiated signal that is required for in vivo growth of a human carcinoma
EGFR is a transducer of the urokinase receptor initiated signal that is required for in vivo growth of a human carcinoma
复制标题
DOI：
10.1016/s1535-6108(02)00072-7
复制
发表时间：
2002-06-01
期刊：
影响因子：
50.3
通讯作者：
Ossowski, L
中科院分区：
文献类型：
--
作者：
Liu, D;Ghiso, JAA;Ossowski, L
尿激酶纤溶酶原激活物受体（uPAR）激活α 5 β 1整合素和ERK信号传导，诱导HEp 3人癌的体内增殖。在这里，我们证明，EGFR介导的uPAR/整合素/纤连蛋白（FIN）诱导的生长途径。它的激活是配体非依赖性的，不需要高EGFR，但需要高uPAR表达。只有当uPAR水平组成性升高时，EGFR才与α 5 β 1相关并被激活。uPAR的结构域1对于EGFR活化至关重要，并且FAK连接整合素和EGFR信号传导。抑制EGFR激酶阻断uPAR诱导的ERK信号，暗示EGFR是该途径的重要效应子。uPAR或EGFR信号传导的破坏降低体内HEp 3增殖。这些发现揭示了uPAR颠覆配体调节的EGFR信号传导的机制，为癌细胞提供增殖优势。
Urokinase plasminogen activator receptor (uPAR) activates alpha5beta1 integrin and ERK signaling, inducing in vivo proliferation of HEp3 human carcinoma. Here we demonstrate that EGFR mediates the uPAR/integrin/fibronectin (FIN) induced growth pathway. Its activation is ligand-independent and does not require high EGFR, but does require high uPAR expression. Only when uPAR level is constitutively elevated does EGFR become alpha5beta1-associated and activated. Domain 1 of uPAR is crucial for EGFR activation, and FAK links integrin and EGFR signaling. Inhibition of EGFR kinase blocks uPAR induced signal to ERK, implicating EGFR as an important effector of the pathway. Disruption of uPAR or EGFR signaling reduces HEp3 proliferation in vivo. These findings unveil a mechanism whereby uPAR subverts ligand-regulated EGFR signaling, providing cancer cells with proliferative advantage.