Interrogation of Functional Cell-Surface Markers Identifies CD151 Dependency in High- Grade Serous Ovarian Cancer
Interrogation of Functional Cell-Surface Markers Identifies CD151 Dependency in High- Grade Serous Ovarian Cancer
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DOI：
10.1016/j.celrep.2017.02.028
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发表时间：
2017-03-07
期刊：
影响因子：
8.8
通讯作者：
Rottapel, Robert
中科院分区：
文献类型：
--
作者：
Medrano, Mauricio;Communal, Laudine;Rottapel, Robert
高级别浆液性卵巢癌(HGSC)的遗传变异程度使识别驱动肿瘤进展的分子特征变得困难。在这里，我们在一组HGSC细胞系中进行全基因组RNAi筛选和细胞表面标记的全面表达分析，以确定对它们的生存至关重要的基因。我们报道，Tetraspanin CD151有助于与ZeB转录程序相关的HGSC细胞亚群的存活，并支持HGSC肿瘤的生长。此外，我们还表明CD151的高表达预示着不良的临床预后。这项研究揭示了与HGSC相关的细胞表面脆弱性，提供了一个识别治疗靶点的框架，并报告了CD151在HGSC中的作用。
The degree of genetic aberrations characteristic of high-grade serous ovarian cancer (HGSC) makes identification of the molecular features that drive tumor progression difficult. Here, we perform genomewide RNAi screens and comprehensive expression analysis of cell-surface markers in a panel of HGSC cell lines to identify genes that are critical to their survival. We report that the tetraspanin CD151 contributes to survival of a subset of HGSC cell lines associated with a ZEB transcriptional program and supports the growth of HGSC tumors. Moreover, we show that high CD151 expression is prognostic of poor clinical outcome. This study reveals cell-surface vulnerabilities associated with HGSC, provides a framework for identifying therapeutic targets, and reports a role for CD151 in HGSC.