GCF2 Promotes Cancer Metastasis and Invasion through its interaction with Deshevelled

GCF2通过与Deshevelled相互作用促进癌症转移和侵袭

• 批准号: 20689025
• 负责人: OHTSUKA Hideo
• 金额: $ 10.9万
• 依托单位: Tohoku University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Young Scientists (A)
• 财政年份: 2008
• 资助国家: 日本
• 起止时间: 2008 至 2011
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-20689025/
• 关键词: GCF2; LRRFIP1; Dishevelled; RhoA; シグナル伝達; 癌; 外科; LRRFIPI; Dishevelle

A recent comprehensive analysis of human cancer has demonstrated that GCF2/LRRFIP1 is one of the cancer associated genes that are categorized as transcriptional regulators. Up to now, however, the precise relationship between the GCF2 expression and carcinogenesis has not been established. Recently, a new function of GCF2 as a regulator of cell migration through the RhoA activity was identified. From these works, I hypothesized that GCF2 may regulate cancer cell invasion or metastasis. To clarify the metastatic potential of GCF2 in colorectal cancer, I established HT-29 cells stably suppressing the GCF2 expression and injected them into the spleen of the SCID mouse. In this work, we found GCF2 suppression reduced the number of liver metastases. Furthermore, mechanistic analyses indicated that the inhibition of GCF2 reduced the fibronectin induced cell adhesion, migration and invasion activities. Downstream the integrin signaling pathways, GCF2 regulate the activity of RhoA interacting with the RGS domain of Leukemia associated RhoGEF (LARG). These results suggest that GCF2 has an important role in colorectal cancer cells metastasis regulating the RhoA induced cell adhesion, migration and invasion activity.

最近对人类癌症的综合分析表明，GCF 2/LRRFIP 1是被归类为转录调节因子的癌症相关基因之一。然而，到目前为止，GCF 2的表达和癌变之间的确切关系尚未建立。最近，GCF 2作为通过RhoA活性的细胞迁移调节剂的新功能被鉴定。从这些工作中，我假设GCF 2可能调节癌细胞的侵袭或转移。为了阐明GCF 2在结直肠癌中的转移潜力，我建立了稳定抑制GCF 2表达的HT-29细胞，并将它们注射到SCID小鼠的脾脏中。在这项工作中，我们发现GCF 2抑制减少了肝转移的数量。此外，机制分析表明，GCF 2的抑制降低了纤维连接蛋白诱导的细胞粘附，迁移和侵袭活动。在整合素信号通路下游，GCF 2调节RhoA与白血病相关RhoGEF（LARG）的RGS结构域相互作用的活性。这些结果表明GCF 2在调节RhoA诱导的细胞粘附、迁移和侵袭活性中具有重要作用。

项目成果

GC binding factor 2(GCF 2)regulates the activation of small GTP-binding protein, Rho A

GC 结合因子 2 (GCF 2) 调节小 GTP 结合蛋白 Rho A 的激活

• 发表时间: 2008
• 作者: Hideo Ohtsuka;et.al.
• 通讯作者: et.al.

AC. GC-binding factor 2 interacts with dishevelled and regulates Wnt signaling pathways in human carcinoma cell lines

交流电。

• 发表时间: 2011
• 期刊: Int J Cancer
• 影响因子: 6.4
• 作者: Ohtsuka H;Oikawa M;Ariake K;Rikiyama T;Motoi F;Katayose Y;Unno M;Johnson
• 通讯作者: Johnson

GCF2 interacts with Dishevelled and regulates the activation of RhoA in carcinoma cells.

GCF2 与 Disheveled 相互作用并调节癌细胞中 RhoA 的激活。

• 发表时间: 2011
• 期刊: Int.J.Cancer
• 作者: Ohtsuka H;Oikawa M;et al.
• 通讯作者: et al.

GCF2/LRRFIP1 Controls Extravasation Of Colorectal Cancer Cells and Formation Of Liver Metastasis Regulating The Activation Of RhoA

GCF2/LRRFIP1 控制结直肠癌细胞的外渗和肝转移的形成，调节 RhoA 的激活

• 发表时间: 2011
• 作者: Kyohei Ariake;Hideo Ohtsuka;Fuyuhiko Motoi;Toshiki Rikiyama;Yu Katayose;Shinichi Egawa;Michiaki Unno.
• 通讯作者: Michiaki Unno.

新規RhoA活性化調節因子GC-binding factor 2(GCF2)による, 消化器癌浸潤・転移制御の可能性

新型RhoA激活调节剂GC结合因子2（GCF2）控制胃肠道癌症侵袭和转移的可能性

• 发表时间: 2010
• 作者: 有明恭平;大塚英郎;元井冬彦;力山敏樹;片寄友;江川新一;海野倫明
• 通讯作者: 海野倫明