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

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

Author information

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: rottapel@uhnresearch.ca.

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

PMID:
28273451
DOI:
10.1016/j.celrep.2017.02.028
[Indexed for MEDLINE]
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