Medrano Mauricio, Communal Laudine, Brown Kevin R, Iwanicki Marcin, Normand Josee, Paterson Joshua, Sircoulomb Fabrice, Krzyzanowski Paul, Novak Marian, Doodnauth Sasha A, Saiz Fernando Suarez, Cullis Jane, Al-Awar Rima, Neel Benjamin G, McPherson John, Drapkin Ronny, Ailles Laurie, Mes-Massons Anne-Marie, Rottapel Robert
Princess Margaret Cancer Center, University Health Network, Toronto, ON M5G 1L7, Canada; Department of Medical Biophysics, University of Toronto, Toronto, ON M5G 1L7, Canada.
Centre de Recherche du Centre Hospitalier de l'Université de Montréal (CRCHUM), Montreal, QC H2X 0A9, Canada; Institut du Cancer de Montréal, Montréal, QC H2X 0A9, Canada.
Cell Rep. 2017 Mar 7;18(10):2343-2358. doi: 10.1016/j.celrep.2017.02.028.
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 genome-wide 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.
高级别浆液性卵巢癌（HGSC）所特有的基因畸变程度使得确定驱动肿瘤进展的分子特征变得困难。在此，我们对一组HGSC细胞系进行全基因组RNA干扰筛选和细胞表面标志物的综合表达分析，以鉴定对其生存至关重要的基因。我们报告，四跨膜蛋白CD151有助于与ZEB转录程序相关的一部分HGSC细胞系的生存，并支持HGSC肿瘤的生长。此外，我们表明高CD151表达预示着不良的临床结果。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。
