尿激酶受体与肿瘤转移的关系研究进展  

Research progress of the relationship between urokinase receptor in tumor progression and development

作　　者：王合兵[1] 肖坚[1] 陈文新[1] 杨炳林[1] 

机构地区：[1]福建医科大学附属三明第一医院乳腺科,福建三明365000

出　　处：《中华临床医师杂志（电子版）》2014年第13期141-145,共5页Chinese Journal of Clinicians(Electronic Edition)

摘　　要：尿激酶受体(uPAR)水平升高在不同类型的浸润性肿瘤中大多可检测到,且与肿瘤预后差密切相关。尿激酶(uPA)与uPAR结合触发纤溶酶原转换成纤维蛋白溶酶,继而出现基质金属蛋白酶被激活,降低周围的细胞外基质的成分,从而促进肿瘤细胞的侵袭和转移。uPA-uPAR的相互作用会刺激细胞增殖/生存和促癌基因的表达,从而促进肿瘤的发展。除了与uPA本身的相互作用,uPAR也与玻连蛋白之间相互作用,通过活化Rac和刺激细胞迁移,促进肿瘤的转移。虽然机制尚待阐明,uPAR已经显示出促进上皮-间质转化(EMT)和诱导乳腺癌肿瘤干细胞样的特性。事实上,uPAR与不同的跨膜蛋白,包括整合蛋白、G蛋白偶联受体、生长因子受体在不同肿瘤细胞的相互作用,证明uPAR在肿瘤发生发展中起非常关键的作用。在临床试验的早期阶段研究表明抑制肽阻止uPA-uPAR的相互作用,能延长患者的生存。uPAR的共受体在uPAR的促进肿瘤转移中的重要性表明抗癌治疗药物的发展可通过扰乱uPAR及其功能合作伴侣的相互作用。Elevated level of urokinase receptor （uPAR） is detected in various aggressive cancer types and is closely associated with poor prognosis of cancers. Binding of uPA to uPAR triggers the conversion of plasminogen to plasmin and the subsequent activation of metalloproteinases. These events confer tumor cells with the capability to degrade the components of the surrounding extracellular matrix, thus contributing to tumor cell invasion and metastasis. uPA-uPAR interaction also elicits signals that stimulate cell proliferation/survival and the expression of tumor-promoting genes, thus assisting tumor development. In addition to its interaction with uPA, uPAR also interacts with vitronectin and this interaction promotes cancer metastasis by activating Rac and stimulating cell migration. Although underlying mechanisms are yet to be fully elucidated, uPAR has been shown to facilitate epithelial-mesenchymal transition （EMT） and induce cancer stem cell-like properties in breast cancer cells. The fact that uPAR lacks intracellular domain suggests that its signaling must be mediated through its co-receptors. Indeed, uPAR interacts with diverse transmembrane proteins including integrins, ENDO180, G protein-coupled receptors and growth factor receptors in cancer cells and these interactions are proven to be critical for the role of uPAR in tumorigenesis. Inhibitory peptide that prevents uPA-uPAR interaction has shown the promise to prolong patients’ survival in the early stage of clinical trial. The importance of uPAR’s co-receptor in uPAR’s tumor-promoting effects implicate that anti-cancer therapeutic agents may also be developed by disrupting the interactions between uPAR and its functional partners.

关 键 词：尿纤溶酶原激活物 肿瘤转移 

分 类 号：R730.2[医药卫生—肿瘤]