Suppression of  ABHD2 , identified through a functional genomics screen, causes anoikis resistance, chemoresistance and poor prognosis in ovarian cancer

Koji Yamanoi; Noriomi Matsumura; Susan K. Murphy; Tsukasa Baba; Kaoru Abiko; Junzo Hamanishi; Ken Yamaguchi; Masafumi Koshiyama; Ikuo Konishi; Masaki Mandai

doi:10.18632/oncotarget.9951

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Research Papers:

Suppression of ABHD2, identified through a functional genomics screen, causes anoikis resistance, chemoresistance and poor prognosis in ovarian cancer

Koji Yamanoi _, Noriomi Matsumura, Susan K. Murphy, Tsukasa Baba, Kaoru Abiko, Junzo Hamanishi, Ken Yamaguchi, Masafumi Koshiyama, Ikuo Konishi and Masaki Mandai

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Oncotarget. 2016; 7:47620-47636. https://doi.org/10.18632/oncotarget.9951

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Abstract

Koji Yamanoi1, Noriomi Matsumura1, Susan K. Murphy2, Tsukasa Baba1, Kaoru Abiko1, Junzo Hamanishi1, Ken Yamaguchi1, Masafumi Koshiyama1, Ikuo Konishi1, Masaki Mandai3

1Department of Gynecology and Obstetrics, Kyoto University Graduate School of Medicine, Kyoto, Japan

2Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, Duke University Medical Center, Durham, NC, USA

3Department of Obstetrics and Gynecology, Faculty of Medicine, KinKi University, Osaka, Japan

Correspondence to:

Noriomi Matsumura, email: [email protected]

Keywords: ovarian cancer, anoikis resistance, functional genomics screen, shRNA library

Received: October 12, 2015 Accepted: May 28, 2016 Published: June 13, 2016

ABSTRACT

Anoikis resistance is a hallmark of cancer, and relates to malignant phenotypes, including chemoresistance, cancer stem like phenotypes and dissemination. The aim of this study was to identify key factors contributing to anoikis resistance in ovarian cancer using a functional genomics screen. A library of 81 000 shRNAs targeting 15 000 genes was transduced into OVCA420 cells, followed by incubation in soft agar and colony selection. We found shRNAs directed to ABHD2, ELAC2 and CYB5R3 caused reproducible anoikis resistance. These three genes are deleted in many serous ovarian cancers according to The Cancer Genome Atlas data. Suppression of ABHD2 in OVCA420 cells increased phosphorylated p38 and ERK, platinum resistance, and side population cells (p<0.01, respectively). Conversely, overexpression of ABHD2 decreased resistance to anoikis (p<0.05) and the amount of phosphorylated p38 and ERK in OVCA420 and SKOV3 cells. In clinical serous ovarian cancer specimens, low expression of ABHD2 was associated with platinum resistance and poor prognosis (p<0.05, respectively). In conclusion, we found three novel genes relevant to anoikis resistance in ovarian cancer using a functional genomics screen. Suppression of ABHD2 may promote a malignant phenotype and poor prognosis for women with serous ovarian cancer.

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Research Papers:

Suppression of ABHD2, identified through a functional genomics screen, causes anoikis resistance, chemoresistance and poor prognosis in ovarian cancer

Abstract