Analysis of Par3 complex in advanced and metastatic ovarian cancer and application of establishing a novel EMT inhibitor

• Project/Area Number: 15K10705
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Obstetrics and gynecology
• Research Institution: Teikyo University (2017); The University of Tokyo (2015-2016)
• Principal Investigator: Kazunori Nagasaka 帝京大学, 医学部, 講師 (30624233)
• Project Period (FY): 2015-04-01 – 2018-03-31
• Project Status: Completed (Fiscal Year 2017)
• Budget Amount: ¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000); Fiscal Year 2017: ¥520,000 (Direct Cost: ¥400,000、Indirect Cost: ¥120,000); Fiscal Year 2016: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000); Fiscal Year 2015: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
• Keywords: Par3 / cell polarity / ovarian cancer / metastasis / prognosis / STAT3 / 細胞極性 / 卵巣癌 / 腹膜播種 / IL6/STAT3経路 / Par3蛋白質 / STAT3/IL6経路

Outline of Final Research Achievements

The polarity proteins hScrib and Par3 are key regulators of processes altered in cancer. These cell polarity proteins have been reported to be involved in epithelial-mesenchymal transition (EMT) and cancer invasion. In the study, we investigated the association between Par3 expression level and survival of 50 ovarian cancer patients. Expression array data for ovarian cancer patient samples revealed high Par3 expression was significantly associated with poor prognosis (P=0.0033) and significant association between high Par3 levels and peritoneal dissemination at the time of diagnosis. To investigate the function of Par3 in invasion, the IL-6/STAT3 pathway was analyzed upon Par3 knockdown with RNA interference in ovarian cancer cell lines. Par3 is involved in ovarian cancer progression and metastasis. The underlying mechanism may be that Par3 modulates IL-6 /STAT3 signaling. Par3 could be a candidate for prognostic biomarkers in ovarian cancer in monitoring STAT3 signaling.

Research Products

• [Journal Article] Role of concurrent transcervical resection and curettage (TCR+C) for detecting endometrial cancer (2018)
  • Author(s): K. Nagasaka, Y. Matsumoto, K. Oda, M. Maruyama, M. Ikemura, T. Arimoto, K. Kawana, M. Fukayama, Y. Osuga, T. Fujii, Gynecologic Oncology Group, Endoscopic Surgery Group
  • Journal Title: Eur J Gyneacol Oncol Volume: 2 Pages: 265-270
  • Peer Reviewed / Open Access
• [Journal Article] Oncogenic histone methyltransferase EZH2: A novel prognostic marker with therapeutic potential in endometrial cancer. (2017)
  • Author(s): Oki S, Sone K, Oda K, Hamamoto R, Ikemura M, Maeda D, Takeuchi M, Tanikawa M, Mori-Uchino M, Nagasaka K, Miyasaka A, Kashiyama T, Ikeda Y, Arimoto T, Kuramoto H, Wada-Hiraike O, Kawana K, Fukayama M, Osuga Y, Fujii T.
  • Journal Title: Oncotarget Volume: in press Issue: 25 Pages: 40402-40411
  • DOI: 10.18632/oncotarget.16316
  • NAID: 120007089062
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Polycystic Ovarian Morphology may be a Positive Prognostic Factor in Patients with Endometrial Cancer who Achieved Complete Remission after Fertility-Sparing Therapy with Progestin. (2017)
  • Author(s): Fukui Y, Taguchi A, Adachi K, Sato M, Kawata A, Tanikawa M, Sone K, Mori M, Nagasaka K, Matsumoto Y, Arimoto T, Oda K, Osuga Y, Fujii T.
  • Journal Title: Asian Pac J Cancer Prev Volume: 18 Pages: 3111-3116
  • Peer Reviewed / Open Access
• [Journal Article] Expression of Par3 polarity protein correlates with poor prognosis in ovarian cancer (2016)
  • Author(s): Hiroe Nakamura1, Kazunori Nagasaka1, §, Kei Kawana1, §, Ayumi Taguchi1, Yoshiko Kawata, Yuriko Uehara1, Mitsuyo Yoshida1, Masakazu Sato1, Haruka Nishida1, Asaha Fujimoto1, Tomoko Inoue1, Katsuyuki Adachi1, Takeshi Nagamatsu1, Takahide Arimoto1, Katsutoshi Oda1, Yutaka Osuga1, Tomoyuki Fujii1
  • Journal Title: BMC Cancer Volume: 16 Issue: 1 Pages: 897-897
  • DOI: 10.1186/s12885-016-2929-2
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Presentation] Introduction of HPV testing to improve cervical screening in Japan - A comparison of Japanese and foreign studies - (2017)
  • Author(s): Kazunori Nagasaka
  • Organizer: AOGIN 2017 Tokyo Meeting (Asia-Oceania Research Organisation in Genital Infection and Neoplasia)
  • Int'l Joint Research / Invited
• [Presentation] Usefulness of transcervical resection (TCR) for differential diagnosis of malignant endometrial diseases (2017)
  • Author(s): Kazunori Nagasaka
  • Organizer: 18th APAGE Annual Congress 2017
  • Int'l Joint Research
• [Presentation] MDM2 inhibitor DS-3032b and mTOR inhibitor Everolimus exerts antitumor effect in ovarian and renal cell clear cell carcinomas (2017)
  • Author(s): Yoshiko Kawata, Kazunori Nagasaka
  • Organizer: ASGO 2017
  • Int'l Joint Research
• [Presentation] Antitumor activity of MDM2 inhibitor DS-3032b and mTOR inhibitor Everolimus in clear cell carcinomas (2017)
  • Author(s): Yoshiko Kawata, Kazunori Nagasaka
  • Organizer: 第76回日本癌学会学術総会
  • Int'l Joint Research
• [Presentation] HIGHLY EFFICIENT TRAPPING AND ANALYSIS OF RARE CELLS USING AN ELECTROACTIVE MICROWELL ARRAY WITH BARRIERS (2017)
  • Author(s): Makoto Takeuchi, Kazunori Nagasaka
  • Organizer: The 21st International Conference on Miniaturized Systems for Chemistry and Life Sciences
  • Int'l Joint Research
• [Presentation] Highly Efficient Trapping and Analysis of Rare Cells using an Electroactive Microwell Array with Barriers (2017)
  • Author(s): Makoto Takeuchi, Kazunori Nagasaka
  • Organizer: 第76回日本癌学会学術総会
  • Int'l Joint Research
• [Presentation] Par3 (Partitioning defective 3) polarity protein regulates epithelial mesenchymal transition (EMT) in ovarian cancer cell lines (2015)
  • Author(s): Hiroe Nakamura
  • Organizer: 第74回日本癌学会学術総会
  • Place of Presentation: 名古屋
  • Year and Date: 2015-10-08
• [Presentation] Par3 (Partitioning defective 3) polarity protein regulates epithelial mesenchymal transition (EMT) in ovarian cancer cell lines (2015)
  • Author(s): Hiroe Nakamura
  • Organizer: DNA tumour virus meeting
  • Place of Presentation: Italy
  • Year and Date: 2015-07-21
  • Int'l Joint Research
• [Presentation] 細胞極性蛋白質Par3(Partitioning defective 3)は卵巣癌の上皮間葉転換に関与する (2015)
  • Author(s): 中村寛江
  • Organizer: 第67回日本産科婦人科学会学術講演会
  • Place of Presentation: 横浜
  • Year and Date: 2015-04-09