2013 Fiscal Year Final Research Report
Identification of Gab1 as a novel therapeutic target for hepatocellular carcinoma
| Project/Area Number |
23590974
|
|---|
| Research Category |
Grant-in-Aid for Scientific Research (C)
|
| Allocation Type | Multi-year Fund |
|---|
| Section | 一般 |
|---|
| Research Field |
Gastroenterology
|
|---|
| Research Institution | Osaka University |
|---|
Principal Investigator |
YOSHIDA YUICHI 大阪大学, 医学(系)研究科(研究院), 助教 (30457014)
|
|---|
| Co-Investigator(Kenkyū-buntansha) |
KISO Shinichi 大阪大学, 医学系研究科, 特任准教授 (40335352)
WATABE Kenji 大阪大学, 医学系研究科, 助教 (50379244)
|
|---|
| Project Period (FY) |
2011 – 2013
|
| Keywords | 肝発癌 / シグナル伝達 / Gab1 / 分子標的治療 |
|---|
| Research Abstract |
Recently, a better understanding of molecular pathogenesis regarding hepatocellular carcinoma (HCC), including growth factor or receptor Tyrosine Kinases (RTKs) signaling, has led to the development of the novel molecular target therapy. Grb2-associated binder Gab1 is a scaffolding docking adaptor that amplifies signals downstream of a broad range of growth factors/receptor tyrosine kinases, such as HGF/c-MET- or HB-EGF/EGFR- signaling pathways. Although these signals are implicated in liver carcinogenesis, the roles of Gab1 remain unclear. Here, we investigated the role of Gab1 in HCC and demonstrated that Gab1 regulates the proliferation of HCC cells in vitro and in vivo. Furthermore, hepatocyte-specific deletion of Gab1 in mice resulted in the enhanced liver fibrosis, which is the major cause of HCC in human. Together, our current results indicate the crucial role of Gab1 in hepatocarcinogenesis and that Gab1 could be a novel molecular target for HCC.
|
-
-
-
-
-
-
-
-
-
-
-
-
-
[Presentation] Loss of Gab1 scaffolding adaptor protein in the hepatocytes exacerbates cholestasis-induced liver fibrosis in mice2013
Author(s)
Takashi Kizu, Yuichi Yoshida, Kunimaro Furuta, Satoshi Ogura, Mayumi Egawa, Norihiro Chatani, Mina Hamano, Hisao Ezaki, Yoshihiro Kamada, Shinichi. Kiso, Tetsuo Takehara
Organizer
The 64th Annual Meeting of the American Association for the Study of Liver Diseases
Place of Presentation
Washington, DC, USA(ポスター発表)
Year and Date
2013-11-04
-
[Presentation] Kiso, Akihiko Shimano, Noriyuki Ouchi, Yuichi Yoshida, Tetsuo Takehara Lack of secreted frizzled-related protein 5 (Sfrp5), an adipocytokine, enhanced carbon-tetrachloride-induced liver fibrosis in mice2013
Author(s)
Norihiro Chatani, Yoshihiro Kamada, Takashi Kizu, Satoshi Ogura, Kunimaro Furuta, Mayumi Egawa, Mina Hamano, Hisao Ezaki, Shinichi
Organizer
The 64th Annual Meeting of the American Association for the Study of Liver Diseases
Place of Presentation
Washington, DC, USA(ポスター発表)
Year and Date
2013-11-04
-
[Presentation] Kiso, Tetsuo Takehara Grb2-associated binder 1 docking protein is crucial for mortality in a mouse model of acute liver failure2013
Author(s)
Kunimaro Furuta, Yuichi Yoshida, Takashi Kizu, Satoshi Ogura, Mayumi Egawa, Norihiro Chatani, Mina Hamano, Hisao Ezaki, Yoshihiro Kamada, Shinichi
Organizer
The 64th Annual Meeting of the American Association for the Study of Liver Diseases
Place of Presentation
Washington, DC, USA (Parallel session, 口頭発表)
Year and Date
2013-11-04
-
-
-
-
-
-
[Presentation] Crucial role of FoxM1 transcription factor as a predictor of clinical outcomes in patients with hepatocellular carcinoma2012
Author(s)
Mayumi Egawa, Yuichi Yoshida, Shinichi Kiso, Akira Tomokuni, Takashi Kizu, Kunimaro Furuta, Takayo Takemura, Mina Hamano, Norihiro Chatani, Hisao Ezaki, Yoshihiro Kamada, Hiroaki Nagano, Yuichiro Doki, Masaki Mori, and Tetsuo Takehara
Organizer
The 63rd Annual Meeting of the American Association for the Study of Liver Diseases
Place of Presentation
Hynes Convention Center, Boston, Massachusetts, USA (Parallel session, 口頭発表)
Year and Date
2012-11-12
-
[Presentation] Association of lipid overaccumulation with delayed liver regeneration in mice with simple steatosis2012
Author(s)
Mina Hamano, Hisao Ezaki, Kunimaro Furuta, Mayumi Egawa, Takashi Kizu, Norihiro Chatani, Yoshihiro Kamada, Yuichi Yoshida, Shinichi Kiso, Tetsuo Takehara
Organizer
The 63rd Annual Meeting of the American Association for the Study of Liver Diseases
Place of Presentation
Hynes Convention Center, Boston, Massachusetts, USA(ポスター発表)
Year and Date
2012-11-12
-
-
-
-
-
-
-
-
-
-
[Presentation] Pitavastatin administration ameliorated the progression of steatohepatitis in ovariectomized mice fed with high fat and high cholesterol diet2011
Author(s)
Kamada Y, Kiso S, Yoshida Y, Chatani N, Kizu T,Hamano M, Tsubakio M, Takemura T, Ezaki H, Hayashi N, Tetsuo Takehara
Organizer
The 62nd Annual Meeting of the American Association for the Study of Liver Diseases
Place of Presentation
Moscone West Convention Center, San Francisco, USA(ポスター発表)
Year and Date
2011-11-07
-
[Presentation] Gab1 scaffolding adaptor protein protects from liver fibrosis during chronic liver injury in mice2011
Author(s)
Kizu T, Yoshida Y, Takemura T, Furuta K,Kamada Y, Chatani N, Hamano M, Tsubakio M, Ezaki H, Kiso S, Takehara T
Organizer
The 62nd Annual Meeting of the American Association for the Study of Liver Diseases
Place of Presentation
Moscone West Convention Center, San Francisco, USA(ポスター発表)
Year and Date
2011-11-06
-
-
-
