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

• Published in: Cell reports (Cambridge) 2017-03, Vol.18 (10), p.2343-2358
• Main Authors: 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
• Format: Article
• Language: English
• Subjects: Biomarkers, Tumor - metabolism; CD151; Cell Line, Tumor; Cell Membrane - metabolism; Cell Survival; cell-surface; Cystadenocarcinoma, Serous - metabolism; Cystadenocarcinoma, Serous - pathology; Epithelial Cells - metabolism; Female; Gene Regulatory Networks; high-grade serous ovarian cancer; Humans; mesenchymal subtype; Neoplasm Grading; Ovarian Neoplasms - metabolism; Ovarian Neoplasms - pathology; Phenotype; Prognosis; RNAi screen; Tetraspanin 24 - metabolism; Xenograft Model Antitumor Assays; Zinc Finger E-box Binding Homeobox 2 - metabolism; Zinc Finger E-box-Binding Homeobox 1 - metabolism
• ISSN: 2211-1247; 2211-1247
• 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. [Display omitted] •Pooled genome-wide RNAi screens and cell-surface analysis in HGSC cell lines•A subset of HGSC lines is dependent on tetraspanin CD151 for survival•CD151 supports tumor growth in vivo, and dependency is mediated by ZEB1 and ZEB2•High CD151 expression is associated with poor prognosis in HGSC Medrano et al. conduct whole-genome short hairpin RNA screens in 27 high-grade serous ovarian carcinoma (HGSC) cell lines to identify vulnerabilities in HGSC. Analysis of the cell surface reveals that CD151 is essential for cell survival through a ZEB-dependent mechanism.