摘要
构成纤维蛋白溶解系统的主要蛋白酶受到严格调节。蛋白酶抑制剂靶向纤溶酶,负责纤维蛋白降解的蛋白酶以及将纤溶酶原转化为纤溶酶的蛋白酶,包括组织型纤溶酶原激活剂(tPA)和尿激酶型纤溶酶原激活剂(uPA)。调节纤维蛋白溶解的第二种机制涉及异位相互作用,其将纤溶酶原及其激活剂定位于纤维蛋白,细胞外基质(ECM)蛋白和细胞表面。纤溶酶一旦与细胞表面结合产生,就可以裂解跨膜蛋白,激活生长因子,从ECM蛋白释放生长因子,重塑ECM,激活金属蛋白酶并通过裂解蛋白酶激活受体(PAR)家族的受体触发细胞信号转导。这些过程都与癌症有关。因此,毫不奇怪的是,增加了纤溶酶原激活的催化效率的称为纤溶酶原受体(PlgRs)的结构多样但功能相似的细胞表面蛋白家族因其在癌症中的可能功能和作为抗癌药物的靶点而受到关注。发展。在这篇综述中,我们考虑了四个先前描述的人类癌症中的PlgR,包括:α-烯醇酶,膜联蛋白A2,Plg-RKT和细胞角蛋白8。为了比较PlgR,我们从The Cancer Genome Atlas(TCGA)提取了转录组分析数据,并搜索了PlgR表达与患者生存率之间的相关性。在神经胶质瘤中,特异性PlgR的表达与肿瘤等级相关。在包括胶质母细胞瘤和肝癌在内的许多恶性肿瘤中,α-烯醇酶或膜联蛋白-A2的表达增加与预后不良有关。讨论了这些相关性是否反映了PlgRs作为纤溶酶原或其他活性受体的功能。
关键词: 纤溶酶原,组织型纤溶酶原激活物,尿激酶型纤溶酶原激活物,α-烯醇酶,膜联蛋白-A2,细胞角蛋白8,Plg-RKT,uPAR,LDL受体相关蛋白-1,NMDA受体。
图形摘要
[http://dx.doi.org/10.1160/TH04-12-0842] [PMID: 15841308]
[http://dx.doi.org/10.1111/j.1365-2141.2005.05444.x] [PMID: 15842654]
[http://dx.doi.org/10.1007/s00018-010-0566-5] [PMID: 21136135]
[http://dx.doi.org/10.1016/0003-9861(72)90488-2] [PMID: 5044515]
[PMID: 3403557]
[http://dx.doi.org/10.1002/9780470515457.ch4] [PMID: 9524763]
[http://dx.doi.org/10.1096/fasebj.9.10.7615163] [PMID: 7615163]
[PMID: 7199524]
[PMID: 15769664]
[PMID: 3745161]
[http://dx.doi.org/10.1021/bi00220a034] [PMID: 1847072]
[PMID: 1712017]
[PMID: 8063740]
[http://dx.doi.org/10.1160/TH16-12-0936] [PMID: 28382372]
[http://dx.doi.org/10.1182/blood-2007-03-079392] [PMID: 17690254]
[PMID: 7542667]
[http://dx.doi.org/10.1046/j.1365-2141.1996.7482367.x] [PMID: 8857956]
[http://dx.doi.org/10.1182/blood-2008-11-188938] [PMID: 19897580]
[http://dx.doi.org/10.1182/blood.V82.8.2433.2433] [PMID: 8400293]
[http://dx.doi.org/10.1023/A:1020738620817] [PMID: 9988531]
[http://dx.doi.org/10.1172/JCI19684] [PMID: 14702107]
[http://dx.doi.org/10.1182/blood-2005-07-2636] [PMID: 16493010]
[http://dx.doi.org/10.1056/NEJM199904013401303] [PMID: 10099141]
[http://dx.doi.org/10.1182/blood-2008-08-170837] [PMID: 19182206]
[http://dx.doi.org/10.1111/jth.13532] [PMID: 27714956]
[http://dx.doi.org/10.2741/1184] [PMID: 14766366]
[http://dx.doi.org/10.1016/j.blre.2014.09.003] [PMID: 25294122]
[http://dx.doi.org/10.1038/nrm977] [PMID: 12461559]
[http://dx.doi.org/10.1073/pnas.022652999] [PMID: 11818541]
[http://dx.doi.org/10.1126/science.273.5281.1551] [PMID: 8703217]
[http://dx.doi.org/10.1016/S1535-6108(02)00072-7] [PMID: 12124174]
[http://dx.doi.org/10.1083/jcb.146.1.149] [PMID: 10402467]
[http://dx.doi.org/10.2353/ajpath.2009.081053] [PMID: 19497996]
[http://dx.doi.org/10.1074/jbc.M407069200] [PMID: 15448144]
[http://dx.doi.org/10.1074/jbc.M113.509133] [PMID: 24129569]
[http://dx.doi.org/10.1182/blood-2017-04-780205] [PMID: 28684538]
[http://dx.doi.org/10.1242/jcs.173765] [PMID: 26272917]
[http://dx.doi.org/10.1146/annurev.cb.04.110188.000521] [PMID: 3143380]
[http://dx.doi.org/10.1016/0955-0674(93)90040-W] [PMID: 8240832]
[http://dx.doi.org/10.1155/2012/564259] [PMID: 23097597]
[http://dx.doi.org/10.1038/35025229] [PMID: 11001069]
[http://dx.doi.org/10.1021/bi9824792] [PMID: 10194379]
[http://dx.doi.org/10.1073/pnas.2235594100] [PMID: 14559973]
[http://dx.doi.org/10.1161/01.ATV.0000030200.59331.3F] [PMID: 12231560]
[http://dx.doi.org/10.1074/jbc.M401431200] [PMID: 14973136]
[http://dx.doi.org/10.1074/jbc.M401372200] [PMID: 15247268]
[http://dx.doi.org/10.4049/jimmunol.1400334] [PMID: 25165151]
[http://dx.doi.org/10.2741/A689] [PMID: 11689350]
[http://dx.doi.org/10.1136/gut.2003.026831] [PMID: 15194650]
[http://dx.doi.org/10.1158/1078-0432.CCR-06-0324] [PMID: 17020980]
[http://dx.doi.org/10.18632/oncotarget.3572] [PMID: 25860938]
[http://dx.doi.org/10.4137/CGM.S27335] [PMID: 26279629]
[http://dx.doi.org/10.1186/2162-3619-2-12] [PMID: 23594883]
[http://dx.doi.org/10.1055/s-2008-1079254] [PMID: 18645919]
[http://dx.doi.org/10.1007/s10555-015-9599-4] [PMID: 26573921]
[http://dx.doi.org/10.1182/blood.V90.11.4522] [PMID: 9373263]
[http://dx.doi.org/10.5114/wo.2014.47136] [PMID: 25691825]
[http://dx.doi.org/10.1158/0008-5472.CAN-11-1748] [PMID: 22042827]
[http://dx.doi.org/10.1038/nature01322] [PMID: 12490959]
[http://dx.doi.org/10.1016/j.ygeno.2004.08.010] [PMID: 15533718]
[http://dx.doi.org/10.1186/1476-4598-13-65] [PMID: 24650096]
[http://dx.doi.org/10.1038/s41598-018-21358-1] [PMID: 29445239]
[http://dx.doi.org/10.1126/science.aan2507] [PMID: 28818916]
[http://dx.doi.org/10.1038/s41598-017-04185-8] [PMID: 28630480]
[http://dx.doi.org/10.1074/jbc.271.41.25684] [PMID: 8810346]
[http://dx.doi.org/10.1158/1078-0432.CCR-05-0632] [PMID: 16299229]
[http://dx.doi.org/10.1097/01.BRS.0000109883.18015.B9] [PMID: 14752343]
[http://dx.doi.org/10.2106/JBJS.G.01179] [PMID: 18978408]
[http://dx.doi.org/10.1016/j.ajog.2011.05.015]
[http://dx.doi.org/10.1517/13543784.9.9.2085] [PMID: 11060794]
[PMID: 3791243]
[http://dx.doi.org/10.3109/00016348009155415] [PMID: 7424507]
[http://dx.doi.org/10.3109/00016348609157383] [PMID: 3776488]
[http://dx.doi.org/10.1016/0090-8258(86)90026-0] [PMID: 3710265]