title: Interrogation of Functional Cell-Surface Markers Identifies CD151 Dependency in High-Grade Serous Ovarian Cancer.
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.
authors.affiliation: Princess Margaret Cancer Center, University Health Network, Toronto, ON M5G 1L7, Canada; Department of Medical Biophysics, University of Toronto, Toronto, ON M5G 1L7, Canada.
authors.forename: Mauricio
authors.initials: M
authors.lastname: Medrano
authors.affiliation: 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.
authors.forename: Laudine
authors.initials: L
authors.lastname: Communal
authors.affiliation: Banting and Best Department of Medical Research, Donnelly Centre for Cellular and Biomolecular Research, University of Toronto, Toronto, ON M5S 3E1, Canada.
authors.forename: Kevin R
authors.initials: KR
authors.lastname: Brown
authors.affiliation: Department of Cell Biology, Harvard Medical School, Boston, MA 02115, USA.
authors.forename: Marcin
authors.initials: M
authors.lastname: Iwanicki
authors.affiliation: Princess Margaret Cancer Center, University Health Network, Toronto, ON M5G 1L7, Canada.
authors.forename: Josee
authors.initials: J
authors.lastname: Normand
authors.affiliation: Princess Margaret Cancer Center, University Health Network, Toronto, ON M5G 1L7, Canada.
authors.forename: Joshua
authors.initials: J
authors.lastname: Paterson
authors.affiliation: Princess Margaret Cancer Center, University Health Network, Toronto, ON M5G 1L7, Canada.
authors.forename: Fabrice
authors.initials: F
authors.lastname: Sircoulomb
authors.affiliation: Ontario Institute for Cancer Research, MaRS Centre, Toronto, ON M5G 1L7, Canada.
authors.forename: Paul
authors.initials: P
authors.lastname: Krzyzanowski
authors.affiliation: Department of Medical Oncology, Center for Molecular Oncologic Pathology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA 02215, USA.
authors.forename: Marian
authors.initials: M
authors.lastname: Novak
authors.affiliation: Princess Margaret Cancer Center, University Health Network, Toronto, ON M5G 1L7, Canada; Department of Medical Biophysics, University of Toronto, Toronto, ON M5G 1L7, Canada.
authors.forename: Sasha A
authors.initials: SA
authors.lastname: Doodnauth
authors.affiliation: Princess Margaret Cancer Center, University Health Network, Toronto, ON M5G 1L7, Canada.
authors.forename: Fernando Suarez
authors.initials: FS
authors.lastname: Saiz
authors.affiliation: Department of Biochemistry and Molecular Pharmacology, New York University School of Medicine, New York, NY 10016, USA.
authors.forename: Jane
authors.initials: J
authors.lastname: Cullis
authors.affiliation: Ontario Institute for Cancer Research, MaRS Centre, Toronto, ON M5G 1L7, Canada.
authors.forename: Rima
authors.initials: R
authors.lastname: Al-Awar
authors.affiliation: 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.
authors.forename: Benjamin G
authors.initials: BG
authors.lastname: Neel
authors.affiliation: Ontario Institute for Cancer Research, MaRS Centre, Toronto, ON M5G 1L7, Canada.
authors.forename: John
authors.initials: J
authors.lastname: McPherson
authors.affiliation: Ovarian Cancer Research Center, Department of Obstetrics and Gynecology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
authors.forename: Ronny
authors.initials: R
authors.lastname: Drapkin
authors.affiliation: Princess Margaret Cancer Center, University Health Network, Toronto, ON M5G 1L7, Canada; Department of Medical Biophysics, University of Toronto, Toronto, ON M5G 1L7, Canada.
authors.forename: Laurie
authors.initials: L
authors.lastname: Ailles
authors.affiliation: 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.
authors.forename: Anne-Marie
authors.initials: AM
authors.lastname: Mes-Massons
authors.affiliation: 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.
authors.forename: Robert
authors.initials: R
authors.lastname: Rottapel
mesh_terms: D014408:Biomarkers, Tumor / Q000378:metabolism*; D045744:Cell Line, Tumor; D002462:Cell Membrane / Q000378:metabolism*; D002470:Cell Survival; D018284:Cystadenocarcinoma, Serous / Q000378:metabolism* / Q000473:pathology*; D004847:Epithelial Cells / Q000378:metabolism; D005260:Female; D053263:Gene Regulatory Networks; D006801:Humans; D060787:Neoplasm Grading; D010051:Ovarian Neoplasms / Q000378:metabolism* / Q000473:pathology*; D010641:Phenotype; D011379:Prognosis; D060185:Tetraspanin 24 / Q000378:metabolism*; D023041:Xenograft Model Antitumor Assays; D000074165:Zinc Finger E-box Binding Homeobox 2 / Q000378:metabolism; D000071799:Zinc Finger E-box-Binding Homeobox 1 / Q000378:metabolism
chemical_list: D014408:Biomarkers, Tumor; D060185:Tetraspanin 24; C486307:ZEB1 protein, human; C492363:ZEB2 protein, human; D000074165:Zinc Finger E-box Binding Homeobox 2; D000071799:Zinc Finger E-box-Binding Homeobox 1
keywords: CD151; RNAi screen; cell-surface; high-grade serous ovarian cancer; mesenchymal subtype