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 McPherson; Ronny Drapkin; Laurie Ailles; Anne-Marie Mes-Massons; Robert Rottapel

doi:10.1016/j.celrep.2017.02.028

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

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

Authors

Mauricio Medrano¹, Laudine Communal², Kevin R Brown³, Marcin Iwanicki⁴, Josee Normand⁵, Joshua Paterson⁵, Fabrice Sircoulomb⁵, Paul Krzyzanowski⁶, Marian Novak⁷, Sasha A Doodnauth¹, Fernando Suarez Saiz⁵, Jane Cullis⁸, Rima Al-Awar⁶, Benjamin G Neel⁹, John McPherson⁶, Ronny Drapkin¹⁰, Laurie Ailles¹, Anne-Marie Mes-Massons¹¹, Robert Rottapel¹²

Affiliations

¹ Princess Margaret Cancer Center, University Health Network, Toronto, ON M5G 1L7, Canada; Department of Medical Biophysics, University of Toronto, Toronto, ON M5G 1L7, Canada.
² 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.
³ Banting and Best Department of Medical Research, Donnelly Centre for Cellular and Biomolecular Research, University of Toronto, Toronto, ON M5S 3E1, Canada.
⁴ Department of Cell Biology, Harvard Medical School, Boston, MA 02115, USA.
⁵ Princess Margaret Cancer Center, University Health Network, Toronto, ON M5G 1L7, Canada.
⁶ Ontario Institute for Cancer Research, MaRS Centre, Toronto, ON M5G 1L7, Canada.
⁷ Department of Medical Oncology, Center for Molecular Oncologic Pathology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA 02215, USA.
⁸ Department of Biochemistry and Molecular Pharmacology, New York University School of Medicine, New York, NY 10016, USA.
⁹ Princess Margaret Cancer Center, University Health Network, Toronto, ON M5G 1L7, Canada; Laura and Isaac Perlmutter Cancer Centre, NYU Langone Medical Center, New York, NY 10016, USA.
¹⁰ Ovarian Cancer Research Center, Department of Obstetrics and Gynecology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
¹¹ 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; Département de Médecine, Université de Montréal, Montreal, QC H3T 1J4, Canada.
¹² Princess Margaret Cancer Center, University Health Network, Toronto, ON M5G 1L7, Canada; Department of Medical Biophysics, University of Toronto, Toronto, ON M5G 1L7, Canada; Department of Medicine, University of Toronto, Toronto, ON M5G 2C4, Canada; Department of Immunology, University of Toronto, Toronto, ON M5S 1A8, Canada; Division of Rheumatology, St. Michael's Hospital, Toronto, ON M5B 1W8, Canada. Electronic address: [email protected].

PMID: 28273451
DOI: 10.1016/j.celrep.2017.02.028

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.

Keywords: CD151; RNAi screen; cell-surface; high-grade serous ovarian cancer; mesenchymal subtype.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Biomarkers, Tumor / metabolism*
Cell Line, Tumor
Cell Membrane / metabolism*
Cell Survival
Cystadenocarcinoma, Serous / metabolism*
Cystadenocarcinoma, Serous / pathology*
Epithelial Cells / metabolism
Female
Gene Regulatory Networks
Humans
Neoplasm Grading
Ovarian Neoplasms / metabolism*
Ovarian Neoplasms / pathology*
Phenotype
Prognosis
Tetraspanin 24 / metabolism*
Xenograft Model Antitumor Assays
Zinc Finger E-box Binding Homeobox 2 / metabolism
Zinc Finger E-box-Binding Homeobox 1 / metabolism

Substances

Biomarkers, Tumor
Tetraspanin 24
ZEB1 protein, human
ZEB2 protein, human
Zinc Finger E-box Binding Homeobox 2
Zinc Finger E-box-Binding Homeobox 1