GCF2 Promotes Cancer Metastasis and Invasion through its interaction with Deshevelled

最近对人类癌症的综合分析表明，GCF2/LRRFIP1是被归类为转录调控因子的癌症相关基因之一。然而，到目前为止，GCF2表达与肿瘤发生之间的确切关系还没有建立起来。最近，GCF2通过RhoA活性作为细胞迁移调节因子的新功能被发现。从这些工作中，我推测GCF2可能调节癌细胞的侵袭或转移。为了阐明GCF2在结直肠癌中的转移潜能，我建立了稳定抑制GCF2表达的HT-29细胞，并将它们注射到SCID小鼠的脾中。在这项工作中，我们发现抑制GCF2可以减少肝转移的数量。此外，机制分析表明，GCF2的抑制降低了纤维连接蛋白诱导的细胞黏附、迁移和侵袭活性。在整合素信号通路下游，GCF2调节RhoA的活性，与白血病相关Rhogef(LARG)的RGS结构域相互作用。这些结果表明，GCF2在调控RhoA诱导的细胞黏附、迁移和侵袭活性的结直肠癌细胞转移中起重要作用。

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.