Urokinase receptor and resistance to targeted anticancer agents.
Urokinase receptor and resistance to targeted anticancer agents.
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DOI：
10.3389/fphar.2015.00154
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发表时间：
2015
影响因子：
5.6
通讯作者：
Hu J
中科院分区：
文献类型：
--
作者：
Gonias SL;Hu J
尿激酶受体（uPAR）是GPI锚定的膜蛋白，其调节细胞表面的蛋白酶活性，并且与共受体系统协作，触发细胞信号传导并调节细胞内的基因表达。在正常组织中，uPAR基因表达是有限的;然而，在癌症中，uPAR经常过度表达，并且该基因可能被扩增。通常在肿瘤中发展的缺氧进一步增加癌细胞的uPAR表达。uPAR启动的细胞信号传导促进癌细胞迁移、侵袭、转移、上皮-间充质转化、干细胞样性质、存活和从休眠状态释放。新出现的数据表明uPAR的促存活细胞信号传导活性可能允许癌细胞“逃避”靶向抗癌药物的细胞毒性作用。在此，我们回顾了uPAR的分子特性，负责其在癌细胞中的活性和它的能力，以抵消抗癌药物的活性。
The urokinase receptor (uPAR) is a GPI-anchored membrane protein, which regulates protease activity at the cell surface and, in collaboration with a system of co-receptors, triggers cell-signaling and regulates gene expression within the cell. In normal tissues, uPAR gene expression is limited; however, in cancer, uPAR is frequently over-expressed and the gene may be amplified. Hypoxia, which often develops in tumors, further increases uPAR expression by cancer cells. uPAR-initiated cell-signaling promotes cancer cell migration, invasion, metastasis, epithelial-mesenchymal transition, stem cell-like properties, survival, and release from states of dormancy. Newly emerging data suggest that the pro-survival cell-signaling activity of uPAR may allow cancer cells to “escape” from the cytotoxic effects of targeted anticancer drugs. Herein, we review the molecular properties of uPAR that are responsible for its activity in cancer cells and its ability to counteract the activity of anticancer drugs.