Chemoresistance through acquision of anchorage-independent cell growth in ovarian cancer.

• Project/Area Number: 26670722
• 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: MISE HIROKO 京都大学, 医学(系)研究科(研究院), その他 (90725607)
• Co-Investigator(Kenkyū-buntansha): Matsumura Noriomi 京都大学, 医学研究科器官外科学・婦人科学産科学, 准教授 (20452336) ; Konishi Ikuo 京都大学, 医学研究科器官外科学・婦人科学産科学, 名誉教授 (90192062)
• Project Period (FY): 2014-04-01 – 2016-03-31
• Project Status: Completed (Fiscal Year 2015)
• Budget Amount: ¥3,640,000 (Direct Cost: ¥2,800,000、Indirect Cost: ¥840,000); Fiscal Year 2015: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000); Fiscal Year 2014: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
• Keywords: 卵巣癌 / 機能ゲノミクス / 足場非依存性増殖 / 化学療法抵抗性 / 化学療法感受性 / アノイキス抵抗性 / 機能ゲノミクススクリーニング

Outline of Final Research Achievements

It is known that anchorage-independent growth is a character of cancer cells. However, not all the cancer cells have this ability. In this study, we conducted a functional genomics screening by using an shRNA library. Then we found knockdown of ABHD2 increased the ability of anchorage-independent growth. Additionally, in both clinical samples and cell lines, suppressed expression of ABHD2 was associated with resistance to platinum. These results revealed how DNA aberrations in ovarian cancer cause cancer progression and drug resistance and would be useful to develop a new therapy and a biomarker to select drugs.

Research Products

• [Journal Article] Prediction of taxane and platinum sensitivity in ovarian cancer based on gene expression profiles. (2016)
  • Author(s): Murakami R, Matsumura N, Brown JB, Wang Z, Yamaguchi K, Abiko K, Yoshioka Y, Hamanishi J, Baba T, Koshiyama M, Mandai M, Yamada R, Konishi I.
  • Journal Title: Gynecol Oncol. Volume: 141 Issue: 1 Pages: 49-56
  • DOI: 10.1016/j.ygyno.2016.02.027
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] The BMP signaling pathway leads to enhanced proliferation in serous ovarian cancer-a potential therapeutic target. (2015)
  • Author(s): Peng J, Yoshioka Y, Mandai M, et al
  • Journal Title: Mol Carcinog Volume: Epub ahead of print Issue: 4 Pages: 1-11
  • DOI: 10.1002/mc.22283
  • Peer Reviewed / Open Access
• [Journal Article] Chemotherapy Induces Programmed Cell Death-Ligand 1 Overexpression via the Nuclear Factor-κB to Foster an Immunosuppressive Tumor Microenvironment in Ovarian Cancer. (2015)
  • Author(s): Peng J, Hamanishi J, Matsumura N, Abiko K, Murat K, Baba T, Yamaguchi K, Horikawa N, Hosoe Y, Murphy SK, Konishi I, Mandai M.
  • Journal Title: Cancer Res. Volume: 75 Issue: 23 Pages: 5034-5045
  • DOI: 10.1158/0008-5472.can-14-3098
  • Peer Reviewed
• [Journal Article] Metabolic alterations caused by HNF1β expression in ovarian clear cell carcinoma contribute to cell survival. (2015)
  • Author(s): Amano Y, Mandai M, Yamaguchi K, Matsumura N, Kharma B, Baba T, Abiko K, Hamanishi J, Yoshioka Y, Konishi I.
  • Journal Title: Oncotarget. Volume: 6 Issue: 28 Pages: 26002-26017
  • DOI: 10.18632/oncotarget.4692
  • Peer Reviewed
• [Journal Article] IFN-γ from lymphocytes induces PD-L1 expression and promotes progression of ovarian cancer (2015)
  • Author(s): Abiko K, Matsumura N, Hamanishi J, Horikawa N, Murakami R, Yamaguchi K, Yoshioka Y, Baba T, Konishi I, Mandai M
  • Journal Title: British Journal of Cancer Volume: 未確定 Issue: 9 Pages: 1501-1509
  • DOI: 10.1038/bjc.2015.101
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Invasion of uterine cervical squamous cell carcinoma cells is facilitated by locoregional interaction with cancer-associated fibroblasts via activating transforming growth factor-beta. (2015)
  • Author(s): Nagura M, Matsumura N, Baba T, Murakami R, Kharma B, Hamanishi J, Yamaguchi K, Abiko K, Koshiyama M, Mandai M, et al.
  • Journal Title: Gynecol Oncol Volume: 136 Issue: 1 Pages: 104-111
  • DOI: 10.1016/j.ygyno.2014.11.075
  • Peer Reviewed / Open Access
• [Journal Article] Epigenetic and genetic dispositions of ovarian carcinomas. (2014)
  • Author(s): Yamaguchi K, Matsumura N, Mandai M, Baba T, Konishi I, Murphy SK.
  • Journal Title: Oncoscience. Volume: 1 Pages: 574-579
  • Peer Reviewed / Open Access
• [Journal Article] STAT1 drives tumor progression in serous papillary endometrial cancer. (2014)
  • Author(s): Kharma B, Baba T, Matsumura N, Kang HS, Hamanishi J, Murakami R, McConechy MM, Leung S, Yamaguchi K, Hosoe Y, Yoshioka Y, Murphy SK, Mandai M, Huntsman DG, Konishi I.
  • Journal Title: Cancer Res. Volume: 74 Issue: 22 Pages: 6519-6530
  • DOI: 10.1158/0008-5472.can-14-0847
  • Peer Reviewed / Open Access
• [Journal Article] Epigenetic determinants of ovarian clear cell carcinoma biology. (2013)
  • Author(s): Yamaguchi K, Huang Z, Matsumura N, Mandai M, Okamoto T, Baba T, Konishi I, Berchuck A, Murphy SK.
  • Journal Title: Int J Cancer. Volume: - Issue: 3 Pages: 585-97
  • DOI: 10.1002/ijc.28701
  • Peer Reviewed / Open Access
• [Presentation] Functional genomics screening for anoikis resistance in serous ovarian cancer identifies a novel gene ABHD2 (2015)
  • Author(s): Koji Yamanoi, Noriomi Matsumura, Kaoru Abiko, Ken Yamaguchi, Yumiko Yoshioka, Jyunzo Hamanishi, Tsukasa Baba, Masafumi, Koshiyama, Ikuo Konishi
  • Organizer: 第74回日本学会学術総会
  • Place of Presentation: 名古屋国際会議場(名古屋市)
  • Year and Date: 2015-10-08
• [Presentation] 機能ゲノミクススクリーニングによる、卵巣癌のanoikis抵抗性をもたらす因子の同定 (2015)
  • Author(s): 山ノ井康二、松村謙臣、安彦郁、山口建、吉岡弓子、濱西潤三、馬場長、越山雅文、小西郁生、万代昌紀
  • Organizer: 第57回日本婦人科腫瘍学会学術講演会
  • Place of Presentation: アイーナいわて県民情報交流センター(盛岡市)
  • Year and Date: 2015-08-07
• [Presentation] 卵巣癌細胞のanoikis抵抗性を指標とした機能的ゲノミクススクリーニングにより同定されたABHD2の発現低下は，卵巣癌の化学療法耐性をもたらし予後不良因子となる (2015)
  • Author(s): 山ノ井 康二, 松村 謙臣, 安彦 郁, 山口 建, 吉岡 弓子, 濱西 潤三, 馬場 長, 越山 雅文, 小西 郁生
  • Organizer: 第67回日本産科婦人科学会学術講演会
  • Place of Presentation: パシフィコ横浜
  • Year and Date: 2015-04-09 – 2015-04-12
• [Presentation] 卵巣癌細胞のanoikis抵抗性を指標とした機能的ゲノミクススクリーニングにより同定されたABHD2の発現低下は，卵巣癌の化学療法耐性をもたらし予後不良因子となる (2015)
  • Author(s): 山ノ井 康二, 松村 謙臣, 安彦 郁, 山口 建, 吉岡 弓子, 濱西 潤三, 馬場 長, 越山 雅文, 小西 郁生
  • Organizer: 第67回日本産科婦人科学会学術講演会
  • Place of Presentation: パシフィコ横浜(横浜市)
  • Year and Date: 2015-04-09
• [Presentation] Suppression of ABHD2 causes resistance to anoikis, increase of side population and chemoresistance in ovarian cancer. (2014)
  • Author(s): 山ノ井康二、松村謙臣、安彦郁、山口建、吉岡弓子、濱西潤三、馬場長、越山雅文、小西郁生
  • Organizer: 第73回日本癌学会学術総会
  • Place of Presentation: パシフィコ横浜
  • Year and Date: 2014-09-25 – 2014-09-27
• [Presentation] 卵巣癌のanoikis抵抗性に関わる新規遺伝子の探索：ELAC2は化学療法耐性にも寄与する (2014)
  • Author(s): 山ノ井康二、松村謙臣、安彦郁、山口建、吉岡弓子、濱西潤三、馬場長、越山雅文、小西郁生
  • Organizer: 第56回日本婦人科腫瘍学会学術講演会
  • Place of Presentation: 栃木県総合分化センター
  • Year and Date: 2014-07-17 – 2014-07-19
• [Book] 「high-grade 漿液性腺癌のゲノム多様性について」 臨床婦人科産科 69巻1号 (2015)
  • Author(s): 松村謙臣、小西郁生
  • Publisher: 医学書院
• [Book] 「卵巣癌の化学療法感受性と治療個別化」 産婦人科の実際 63巻7号 (2014)
  • Author(s): 松村謙臣、村上隆介、小西郁生
  • Publisher: 金原出版