In vivo functional genomics screen reveals mechanism of peritoneal dissemination in ovarian cancer

• Project/Area Number: 16K15706
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Obstetrics and gynecology
• Research Institution: Kyoto University
• Principal Investigator: Konishi Ikuo 京都大学, 医学研究科, 名誉教授 (90192062)
• Co-Investigator(Kenkyū-buntansha): 松村 謙臣 近畿大学, 医学部, 教授 (20452336) ; 安彦 郁 京都大学, 医学(系)研究科(研究院), 助教 (20508246) ; 濱西 潤三 京都大学, 医学研究科, 講師 (80378736)
• Project Period (FY): 2016-04-01 – 2018-03-31
• Project Status: Completed (Fiscal Year 2017)
• Budget Amount: ¥3,380,000 (Direct Cost: ¥2,600,000、Indirect Cost: ¥780,000); Fiscal Year 2017: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2016: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
• Keywords: 卵巣癌 / 癌幹細胞 / 腹膜播種 / 機能ゲノミクススクリーニング

Outline of Final Research Achievements

A library of 81 000 shRNAs targeting 15 000 human genes was stably transfected to ovarian cancer cell lines. By functional screening of these cancer cells, we screened genes that are responsible for anoikis resistance when down-regulated. One of the screened genes was ABHD2, which was fuctionally related to cisplatin resistance. Furthermore, we identified genes that increase Side Population cells when down-regulated. Side Population cells are defined as cells which have ability to efflux Hoechst 33342. Down-regulation of these genes were related to cancer stemness phenotype.

Research Products

• [Journal Article] Suppression of ABHD2, identified through a functional genomics screen, causes anoikis resistance, chemoresistance and poor prognosis in ovarian cancer. (2016)
  • Author(s): Yamanoi K, Matsumura N, Murphy SK, Baba T, Abiko K, Hamanishi J, Yamaguchi K, Koshiyama M, Konishi I, Mandai M.
  • Journal Title: Oncotarget. Volume: Jul 26;7(30) Issue: 30 Pages: 47620-47636
  • DOI: 10.18632/oncotarget.9951
  • NAID: 120005820858
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Presentation] 機能的ゲノミクススクリーンによる、卵巣癌のside population分画を制御する因子の探索 (2017)
  • Author(s): 山ノ井康二
  • Organizer: 生殖医学フォーラム
• [Presentation] 機能的ゲノミクススクリーニングによる、卵巣がんのside population (SP)分画を制御する6遺伝子の同定 (2016)
  • Author(s): 山ノ井康二、松村謙臣、安彦郁、山口建、濱西潤三、馬場長、越山雅文、小西郁生
  • Organizer: 第75回日本癌学会総会
  • Place of Presentation: パシフィコ横浜(横浜市)
  • Year and Date: 2016-10-06
• [Presentation] Identification through a functional genomics screen of factors whose down-regulation enhances the cancer stem cell population in ovarian cancer (2016)
  • Author(s): Koji Yamanoi, Noriomi Matsumura, Kaoru Abiko, Ken Yamaguchi, Junzo Hamanishi, Tsukasa Baba, Masafumi Koshiyama, Ikuo Konishi
  • Organizer: 第68回日本産科婦人科学会学術講演会
  • Place of Presentation: 東京国際フォーラム(東京都千代田区)
  • Year and Date: 2016-04-21