Identification of Gab1 as a novel therapeutic target for hepatocellular carcinoma

Gab1作为肝细胞癌新治疗靶点的鉴定

• 批准号: 23590974
• 负责人: YOSHIDA YUICHI
• 金额: $ 3.41万
• 依托单位: Osaka University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2011
• 资助国家: 日本
• 起止时间: 2011 至 2013
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-23590974/
• 关键词: 肝発癌; シグナル伝達; Gab1; 分子標的治療; 肝細胞癌; 肝線維化; CCL5; MAP kinase

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.

最近，对肝细胞癌（HCC）的分子发病机制，包括生长因子或受体酪氨酸激酶（RTKs）信号传导的更好理解，导致了新的分子靶向治疗的发展。grb2相关结合物Gab1是一种支架对接适配器，可放大多种生长因子/受体酪氨酸激酶的下游信号，如HGF/c-MET-或HB-EGF/EGFR-信号通路。尽管这些信号与肝癌发生有关，但Gab1的作用尚不清楚。在这里，我们研究了Gab1在HCC中的作用，并证明了Gab1在体外和体内调节HCC细胞的增殖。此外，小鼠肝细胞特异性缺失Gab1导致肝纤维化增强，这是人类HCC的主要原因。总之，我们目前的结果表明Gab1在肝癌发生中的关键作用，并且Gab1可能是HCC的新分子靶点。

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肝細胞癌におけるGab1の関与と肝細胞癌治療の新規分子標的としての可能性

Gab1在肝细胞癌中的参与及其作为肝细胞癌治疗新分子靶点的潜力

• 发表时间: 2011
• 作者: 吉田雄一;木曽真一;椿尾真弓;木津崇;茶谷徳啓;古田訓丸;濱野美奈;竹村貴代;江崎久男;鎌田佳宏;竹原徹郎
• 通讯作者: 竹原徹郎

急性肝不全における肝細胞アダプター蛋白質Gab1の役割

肝细胞衔接蛋白Gab1在急性肝衰竭中的作用

• 发表时间: 2013
• 作者: 古田訓丸;吉田雄一;木津崇;柄川真弓;茶谷徳啓;濱野美奈;江崎久男;鎌田佳宏;木曽真一;竹原徹郎
• 通讯作者: 竹原徹郎

Crucial role of FoxM1 transcription factor as a predictor of clinical outcomes in patients with hepatocellular carcinoma

FoxM1转录因子作为肝细胞癌患者临床结果预测因子的关键作用

• 发表时间: 2012
• 作者: 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
• 通讯作者: and Tetsuo Takehara

Association of lipid overaccumulation with delayed liver regeneration in mice with simple steatosis

单纯性脂肪变性小鼠脂质过度积累与肝再生延迟的关系

• 发表时间: 2012
• 作者: Mina Hamano;Hisao Ezaki;Kunimaro Furuta;Mayumi Egawa;Takashi Kizu;Norihiro Chatani;Yoshihiro Kamada;Yuichi Yoshida;Shinichi Kiso;Tetsuo Takehara
• 通讯作者: Tetsuo Takehara