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

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

University of Toronto
Centre Hospitalier de L'Universite de Montreal
University of Montreal
Ontario Institute for Cancer Research
Harvard University
New York University
University of Pennsylvania

Research output: Contribution to journal › Article › peer-review

34 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 language	English
Pages (from-to)	2343-2358
Number of pages	16
Journal	Cell Reports
Volume	18
Issue number	10
DOIs	https://doi.org/10.1016/j.celrep.2017.02.028
State	Published - 7 Mar 2017

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

SDG 3 Good Health and Well-being

Keywords

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

Access to Document

10.1016/j.celrep.2017.02.028

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., 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

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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.",

keywords = "CD151, RNAi screen, cell-surface, high-grade serous ovarian cancer, mesenchymal subtype",

author = "Mauricio Medrano and Laudine Communal and Brown, \{Kevin R.\} and Marcin Iwanicki and Josee Normand and Joshua Paterson and Fabrice Sircoulomb and Paul Krzyzanowski and Marian Novak and Doodnauth, \{Sasha A.\} and Saiz, \{Fernando Suarez\} and Jane Cullis and Rima Al-awar and Neel, \{Benjamin G.\} and John McPherson and Ronny Drapkin and Laurie Ailles and Mes-Massons, \{Anne Marie\} and Robert Rottapel",

note = "Publisher Copyright: {\textcopyright} 2017 The Authors",

year = "2017",

month = mar,

day = "7",

doi = "10.1016/j.celrep.2017.02.028",

language = "English",

volume = "18",

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Medrano, M, Communal, L, Brown, KR, Iwanicki, M, Normand, J, Paterson, J, Sircoulomb, F, Krzyzanowski, P, Novak, M, Doodnauth, SA, Saiz, FS, Cullis, J, Al-awar, R, Neel, BG, McPherson, J, Drapkin, R, Ailles, L, Mes-Massons, AM & Rottapel, R 2017, 'Interrogation of Functional Cell-Surface Markers Identifies CD151 Dependency in High-Grade Serous Ovarian Cancer', Cell Reports, vol. 18, no. 10, pp. 2343-2358. https://doi.org/10.1016/j.celrep.2017.02.028

TY - JOUR

T1 - Interrogation of Functional Cell-Surface Markers Identifies CD151 Dependency in High-Grade Serous Ovarian Cancer

AU - Medrano, Mauricio

AU - Communal, Laudine

AU - Brown, Kevin R.

AU - Iwanicki, Marcin

AU - Normand, Josee

AU - Paterson, Joshua

AU - Sircoulomb, Fabrice

AU - Krzyzanowski, Paul

AU - Novak, Marian

AU - Doodnauth, Sasha A.

AU - Saiz, Fernando Suarez

AU - Cullis, Jane

AU - Al-awar, Rima

AU - Neel, Benjamin G.

AU - McPherson, John

AU - Drapkin, Ronny

AU - Ailles, Laurie

AU - Mes-Massons, Anne Marie

AU - Rottapel, Robert

PY - 2017/3/7

Y1 - 2017/3/7

N2 - 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.

AB - 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.

KW - CD151

KW - RNAi screen

KW - cell-surface

KW - high-grade serous ovarian cancer

KW - mesenchymal subtype

UR - https://www.scopus.com/pages/publications/85014580000

UR - https://www.scopus.com/pages/publications/85014580000#tab=citedBy

U2 - 10.1016/j.celrep.2017.02.028

DO - 10.1016/j.celrep.2017.02.028

M3 - Article

C2 - 28273451

AN - SCOPUS:85014580000

VL - 18

SP - 2343

EP - 2358

JO - Cell Reports

JF - Cell Reports

IS - 10

ER -

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

Abstract

UN SDGs

Keywords

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