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.

对人类癌症的最新综合分析表明，GCF2/LRRFIP1是被归类为转录调节剂的癌症相关基因之一。然而，到目前为止，尚未建立GCF2表达与癌变之间的确切关系。最近，确定了GCF2作为细胞迁移的调节剂的新功能。从这些作品中，我假设GCF2可以调节癌细胞侵袭或转移。为了阐明GCF2在大肠癌中的转移潜力，我建立了稳定抑制GCF2表达的HT-29细胞，并将其注入SCID小鼠的脾脏。在这项工作中，我们发现GCF2抑制减少了肝转移的数量。此外，机械分析表明，GCF2的抑制减少了纤连蛋白诱导的细胞粘附，迁移和侵袭活性。在整联蛋白信号通路下游，GCF2调节Rhoa与白血病相关的RGS域相互作用的活性（LARG）。这些结果表明，GCF2在调节RhoA诱导的细胞粘附，迁移和侵袭活性的结直肠癌细胞转移中具有重要作用。

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.

癌細胞の細胞運動における新規Dishevelled関連蛋白 : GCF 2/LRRFIP 1の機能解析

癌细胞细胞运动中的新型蓬乱相关蛋白：GCF 2/LRRFIP 1 的功能分析

• 发表时间: 2008
• 作者: 大塚英郎;他
• 通讯作者: 他

癌細胞の細胞運動における新規Dishevelled関連蛋白: GCF2/LRRFIP1の機能解析.(ワークショップ)

癌细胞细胞运动中的新型蓬乱相关蛋白：GCF2/LRRFIP1 的功能分析（研讨会）。

• 发表时间: 2008
• 作者: 大塚英郎;及川昌也;力山敏樹;片寄友;江川新一;海野倫明
• 通讯作者: 海野倫明

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.