The role of GPCR signaling in gynecologic cancer progression

• Project/Area Number: 26861332
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Obstetrics and gynecology
• Research Institution: Kyushu University
• Principal Investigator: Hiroshi Yagi 九州大学, 医学(系)研究科(研究院), 助教 (70623552)
• Project Period (FY): 2014-04-01 – 2016-03-31
• Project Status: Completed (Fiscal Year 2015)
• Budget Amount: ¥3,770,000 (Direct Cost: ¥2,900,000、Indirect Cost: ¥870,000); Fiscal Year 2015: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2014: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
• Keywords: GPCR / 卵巣癌 / シグナル伝達 / Rho / 転移 / 細胞増殖

Outline of Final Research Achievements

Cancer cells can co-opt the activity of G protein coupled receptors (GPCRs) signaling. Recent analyses revealed that not only GPCRs or its ligands, but also heterotrimeric G proteins play critical roles in cancer progression. Among G proteins, we have focused on G12/13. In immunohistochemical analysis, G12/13 is highly expressed in ovarian cancer tissues. Increased expression of G13 promotes cell proliferation in vitro and tumor grwoth in vivo. To further examine underlying mechanisms of G13-regulated cell proliferation, we took advantage of synthetic biology approach using mutant GPCR and G protein. Detailed analysis revealed that the activation of G13 induces dephosphorylation and nuclear translocation of YAP, which is a core component of Hippo pathway. In addition, inhibition of YAP activity by shRNA or specific inhibitor blocked proliferation of ovarian cancer cells. These data represents G13-YAP signaling axis as a novel therapeutic target of ovarian cancer.

Research Products

• [Journal Article] GEP oncogene promotes cell proliferation through YAP activation in ovarian cancer. (2016)
  • Author(s): Yagi H, Asanoma K, Ohgami T, Ichinoe A, Sonoda K, Kato K.
  • Journal Title: Oncogene Volume: 10 Pages: 1-10
  • DOI: 10.1038/onc.2015.505
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Tumor-To-Tumor Metastasis of Poorly Differentiated Gastric Carcinoma to Uterine Lipoleiomyoma (2015)
  • Author(s): Kiyokoba R, Yagi H, Yahata H, Kawano Y, Kaneki E, Okugawa K, Sonoda K, Kato K.
  • Journal Title: Case Rep Obstet Gynecol Volume: 352369 Pages: 1-6
  • DOI: 10.1155/2015/352369
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Identification of the Critical Site of Calponin 1 for Suppression of Ovarian Cancer Properties (2015)
  • Author(s): Yamane T, Asanoma K, Kobayashi H, Liu G, Yagi H, Ohgami T, Ichinoe A, Sonoda K, Wake N, Kato K.
  • Journal Title: Anticancer Res Volume: 35 Pages: 5993-9
  • Peer Reviewed
• [Journal Article] Regulation of the Mechanism of TWIST1 Transcription by BHLHE40 and BHLHE41 in Cancer Cells (2015)
  • Author(s): Okamoto K, Tsunematsu R, Tahira T, Sonoda K, Asanoma K, Yagi H, Yoneda T, Hayashi K, Wake N, Kato K
  • Journal Title: BMC Med Genet Volume: 16 Pages: 4096-109
  • DOI: 10.1186/s12881-015-0216-8
  • Peer Reviewed / Open Access
• [Journal Article] Uterine myxoid leiomyosarcoma with tumor embolism extending into the right atrium. (2015)
  • Author(s): Hiromi Imai, Hiroshi Yagi, Kaoru Okugawa, Hironori Kenjo, Tatsuhiro Ohgami, Yoshiaki Kawano, Eisuke Kaneki, Akimasa Ichinoe, Kazuo Asanoma, Hideaki Yahata, Kenzo Sonoda, Hiroaki Kobayashi, Tsunehisa Kaku, Kiyoko Kato
  • Journal Title: Case Rep Obstet Gynecol Volume: 2015 Pages: 316262-316262
  • DOI: 10.1155/2015/316262
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Pre-clinical study of BK-UM, a novel inhibitor of HB-EGF, for ovarian cancer therapy. (2014)
  • Author(s): Pre-clinical study of BK-UM, a novel inhibitor of HB-EGF, for ovarian cancer therapy. Nam SO, Yotsumoto F, Miyata K, Suzaki Y, Yagi H, Odawara T, Manabe S, Ishikawa T, Kuroki M, Mekada E, Miyamoto S.
  • Journal Title: Anticancer Res Volume: 34 Pages: 4615-20
  • Peer Reviewed / Open Access
• [Presentation] The G12/13-YAP signaling axis driving proliferation of ovarian cancer cells (2015)
  • Author(s): Hiroshi Yagi, Kenzo Sonoda, Kiyoko Kato
  • 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
• [Presentation] The role of GEP oncogene, Ga12 and Ga13, in the progression of ovarian cancer (2014)
  • Author(s): Yagi H, Sonoda K, Kato K
  • Organizer: 第73回日本癌学会学術総会
  • Place of Presentation: 横浜
  • Year and Date: 2014-09-25 – 2014-09-27
• [Presentation] The role of GEP oncogene, Ga12 and Ga13, in the progression of ovarian cancer (2014)
  • Author(s): Yagi H, Sonoda K, Kato K
  • Organizer: 第66回日本産科婦人科学会学術講演会
  • Place of Presentation: 東京
  • Year and Date: 2014-04-18 – 2014-04-20