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

Publication date: 7 March 2017
Source:Cell Reports, Volume 18, Issue 10
Author(s): Mauricio Medrano, Laudine Communal, Kevin R. Brown, Marcin Iwanicki, Josee Normand, Joshua Paterson, Fabrice Sircoulomb, Paul Krzyzanowski, Marian Novak, Sasha A. Doodnauth, Fernando Suarez Saiz, Jane Cullis, Rima Al-awar, Benjamin G. Neel, John McPherson, Ronny Drapkin, Laurie Ailles, Anne-Marie Mes-Massons, Robert Rottapel
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.

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Teaser

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.


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