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
Affiliations
Mauricio Medrano
Princess Margaret Cancer Center, University Health Network, Toronto, ON M5G 1L7, Canada
Laudine Communal
Centre de Recherche du Centre Hospitalier de l’Université de Montréal (CRCHUM), Montreal, QC H2X 0A9, Canada
Kevin R. Brown
Banting and Best Department of Medical Research, Donnelly Centre for Cellular and Biomolecular Research, University of Toronto, Toronto, ON M5S 3E1, Canada
Marcin Iwanicki
Department of Cell Biology, Harvard Medical School, Boston, MA 02115, USA
Josee Normand
Princess Margaret Cancer Center, University Health Network, Toronto, ON M5G 1L7, Canada
Joshua Paterson
Princess Margaret Cancer Center, University Health Network, Toronto, ON M5G 1L7, Canada
Fabrice Sircoulomb
Princess Margaret Cancer Center, University Health Network, Toronto, ON M5G 1L7, Canada
Paul Krzyzanowski
Ontario Institute for Cancer Research, MaRS Centre, Toronto, ON M5G 1L7, Canada
Marian Novak
Department of Medical Oncology, Center for Molecular Oncologic Pathology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA 02215, USA
Sasha A. Doodnauth
Princess Margaret Cancer Center, University Health Network, Toronto, ON M5G 1L7, Canada
Fernando Suarez Saiz
Princess Margaret Cancer Center, University Health Network, Toronto, ON M5G 1L7, Canada
Jane Cullis
Department of Biochemistry and Molecular Pharmacology, New York University School of Medicine, New York, NY 10016, USA
Rima Al-awar
Ontario Institute for Cancer Research, MaRS Centre, Toronto, ON M5G 1L7, Canada
Benjamin G. Neel
Princess Margaret Cancer Center, University Health Network, Toronto, ON M5G 1L7, Canada
John McPherson
Ontario Institute for Cancer Research, MaRS Centre, Toronto, ON M5G 1L7, Canada
Ronny Drapkin
Ovarian Cancer Research Center, Department of Obstetrics and Gynecology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA
Laurie Ailles
Princess Margaret Cancer Center, University Health Network, Toronto, ON M5G 1L7, Canada
Anne-Marie Mes-Massons
Centre de Recherche du Centre Hospitalier de l’Université de Montréal (CRCHUM), Montreal, QC H2X 0A9, Canada
Robert Rottapel
Princess Margaret Cancer Center, University Health Network, Toronto, ON M5G 1L7, Canada
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.
