The role of GPCR signaling in gynecologic cancer progression

2015 Fiscal Year Final Research Report

• 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
• Keywords: GPCR / 卵巣癌 / シグナル伝達

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.

Free Research Field

シグナル伝達