CDC91L1 (PIG-U) is a newly discovered oncogene in human bladder cancer
CDC91L1 (PIG-U) is a newly discovered oncogene in human bladder cancer
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DOI：
10.1038/nm1010
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发表时间：
2004-04-01
期刊：
影响因子：
82.9
通讯作者：
Trink, B
中科院分区：
文献类型：
--
作者：
Guo, ZM;Linn, JF;Trink, B
20q11 - 13的基因组扩增是人类癌症中常见的事件。我们从一位膀胱癌患者中分离出一个位于20q11的胚系易位断裂点。我们鉴定了编码CDC91L1（也称为磷脂酰肌醇聚糖U类（PIG-U），糖基磷脂酰肌醇（GPI）锚定途径中的转酰胺酶复合物单位）的基因CDC91L1，作为其表达受易位影响的唯一基因。CDC91L1在约三分之一的膀胱癌细胞系和原发性肿瘤中扩增并过表达，以及在用人乳头瘤病毒（HPV）E7转化的致癌性尿路上皮细胞中扩增并过表达。在体外和体内强制过表达CDC91L1恶性转化NIH3T3细胞。CDC91L1的过表达还导致尿激酶受体（uPAR）（一种GPI锚定蛋白）的上调，进而增加膀胱癌细胞中STAT-3的磷酸化。我们的研究结果表明，CDC91L1是膀胱癌的癌基因，并暗示GPI锚定系统作为一个潜在的致癌途径和治疗靶点在人类癌症。
Genomic amplification at 20q11-13 is a common event in human cancers. We isolated a germline translocation breakpoint at 20q11 from a bladder cancer patient. We identified CDC91L1, the gene encoding CDC91L1 (also called phosphatidylinositol glycan class U (PIG-U), a transamidase complex unit in the glycosylphosphatidylinositol (GPI) anchoring pathway), as the only gene whose expression was affected by the translocation. CDC91L1 was amplified and overexpressed in about one-third of bladder cancer cell lines and primary tumors, as well as in oncogenic uroepithelial cells transformed with human papillomavirus (HPV) E7. Forced overexpression of CDC91L1 malignantly transformed NIH3T3 cells in vitro and in vivo. Overexpression of CDC91L1 also resulted in upregulation of the urokinase receptor (uPAR), a GPI-anchored protein, and in turn increased STAT-3 phosphorylation in bladder cancer cells. Our findings suggest that CDC91L1 is an oncogene in bladder cancer, and implicate the GPI anchoring system as a potential oncogenic pathway and therapeutic target in human cancers.