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

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 Douglas Mcpherson, Ronny Drapkin, Laurie Ailles, Anne Marie Mes-Massons, Robert Rottapel

Research output: Contribution to journalArticle

12 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)2343-2358
Number of pages16
JournalCell Reports
Volume18
Issue number10
DOIs
StatePublished - Mar 7 2017
Externally publishedYes

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Keywords

  • CD151
  • cell-surface
  • high-grade serous ovarian cancer
  • mesenchymal subtype
  • RNAi screen

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

Medrano, M., Communal, L., Brown, K. R., Iwanicki, M., Normand, J., Paterson, J., Sircoulomb, F., Krzyzanowski, P., Novak, M., Doodnauth, S. A., Saiz, F. S., Cullis, J., Al-awar, R., Neel, B. G., Mcpherson, J. D., Drapkin, R., Ailles, L., Mes-Massons, A. M., & Rottapel, R. (2017). Interrogation of Functional Cell-Surface Markers Identifies CD151 Dependency in High-Grade Serous Ovarian Cancer. Cell Reports, 18(10), 2343-2358. https://doi.org/10.1016/j.celrep.2017.02.028