The role of GPCR signaling in gynecologic cancer progression
Project/Area Number |
26861332
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Research Category |
Grant-in-Aid for Young Scientists (B)
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Allocation Type | Multi-year Fund |
Research Field |
Obstetrics and gynecology
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Research Institution | Kyushu University |
Principal Investigator |
Hiroshi Yagi 九州大学, 医学(系)研究科(研究院), 助教 (70623552)
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Project Period (FY) |
2014-04-01 – 2016-03-31
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Project Status |
Completed (Fiscal Year 2015)
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Budget Amount *help |
¥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.
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Report
(3 results)
Research Products
(11 results)
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[Journal Article] Regulation of the Mechanism of TWIST1 Transcription by BHLHE40 and BHLHE41 in Cancer Cells2015
Author(s)
Asanoma K, Liu G, Yamane T, Miyanari Y, Takao T, Yagi H, Ohgami T, Ichinoe A, Sonoda K, Wake N, Kato K.
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Journal Title
Mol Cell Biol
Volume: 35
Pages: 4096-109
DOI
Related Report
Peer Reviewed
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[Journal Article] SNP55, a new functional polymorphism of MDM2-P2 promoter, contributes to allele-specific expression of MDM2 in endometrial cancers.2015
Author(s)
Okamoto K, Tsunematsu R, Tahira T, Sonoda K, Asanoma K, Yagi H, Yoneda T, Hayashi K, Wake N, Kato K.
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Journal Title
BMC Med Genet
Volume: 16
Pages: 1-15
DOI
Related Report
Peer Reviewed
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[Journal Article] Uterine myxoid leiomyosarcoma with tumor embolism extending into the right atrium.2015
Author(s)
Imai H, Yagi H, Okugawa K, Kenjo H, Ohgami T, Kawano Y, Kaneki E, Ichinoe A, Asanoma K, Yahata H, Sonoda K, Kobayashi H, Kaku T, Kato K.
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Journal Title
Case Rep Obstet Gynecol
Volume: 316262
Pages: 1-6
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Uterine myxoid leiomyosarcoma with tumor embolism extending into the right atrium2015
Author(s)
Imai H, Yagi H, Okugawa K, Kenjo H, Ohgami T, Kawano Y, Kaneki E, Ichinoe A, Asanoma K, Yahata H, Sonoda K, Kobayashi H, Kaku T, Kato K.
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Journal Title
Case Rep Obstet Gynecol
Volume: 31
Pages: 316262
DOI
Related Report
Peer Reviewed / Open Access
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[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.
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Journal Title
Anticancer Res
Volume: 34
Pages: 4615-20
Related Report
Peer Reviewed / Open Access
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