解开KIAA1199的角色,小说内质网蛋白在癌细胞迁移。
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Evensen NA, Kuscu C, Nguyen HL Zarrabi K,杜福尔,Kadam P,胡锦涛YJ, Pulkoski-Gross, Bahou WF,曹Zucker年代,J
解开KIAA1199的角色,小说内质网蛋白在癌细胞迁移。
中华肿瘤杂志。2013年9月18日,105 (18):1402 - 16。doi: 10.1093 / jnci / djt224。Epub 2013年8月29日。
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23990668 (在PubMed]
- 文摘
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背景:细胞迁移是癌症转移的一个关键决定因素,并更好的理解基因会导致识别旨在预防癌症传播的新靶点。KIAA1199已被证明是调节人类癌症,但它的作用在癌症的发展过程中是迄今未知。方法:临床相关性评估通过检查KIAA1199表达在人类癌症标本。在体外和体内研究了确定KIAA1199癌症发展的功能。细胞定位KIAA1199显微镜下决定。SNAP-tag拉分析被用来识别KIAA1199的约束力的合作伙伴(s)。钙含量进行评估使用spectrofluorometric和荧光共振能量转移分析。信号通路被免疫印迹分析。学生t测试是用来评估的差异。统计测试都是双面的。 RESULTS: KIAA1199 was upregulated in invasive breast cancer specimens and inversely associated with patient survival rate. Silencing of KIAA1199 in MDA-MB-435 cancer cells resulted in a mesenchymal-to-epithelial transition that reduced cell migratory ability in vitro (75% reduction; P < .001) and decreased metastasis in vivo (80% reduction; P < .001). Gain-of-function assays further demonstrated the role of KIAA1199 in cell migration. KIAA1199-enhanced cell migration required endoplasmic reticulum (ER) localization, where it forms a stable complex with the chaperone binding immunoglobulin protein (BiP). A novel ER-retention motif within KIAA1199 that is required for its ER localization, BiP interaction, and enhanced cell migration was identified. Mechanistically, KIAA1199 was found to mediate ER calcium leakage, and the resultant increase in cytosolic calcium ultimately led to protein kinase C alpha activation and cell migration. CONCLUSIONS: KIAA1199 serves as a novel cell migration-promoting gene and plays a critical role in maintaining cancer mesenchymal status.