功能性细胞表面标志物的检测确定了高级别浆液性卵巢癌对CD151的依赖性。

Interrogation of Functional Cell-Surface Markers Identifies CD151 Dependency in High-Grade Serous Ovarian Cancer.

作者信息

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

机构信息

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.

出版信息

Cell Rep. 2017 Mar 7;18(10):2343-2358. doi: 10.1016/j.celrep.2017.02.028.

DOI:10.1016/j.celrep.2017.02.028

PMID:28273451

Abstract

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.

摘要

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。