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GCF2/LRRFIP1 通过整合素依赖性 RhoA 激活促进结直肠癌转移和肝侵袭。

GCF2/LRRFIP1 promotes colorectal cancer metastasis and liver invasion through integrin-dependent RhoA activation.

机构信息

Division of Gastroenterological Surgery, Department of Surgery, Tohoku University, Seiryo-machi, Aoba-ku, Sendai, Japan.

出版信息

Cancer Lett. 2012 Dec 1;325(1):99-107. doi: 10.1016/j.canlet.2012.06.012. Epub 2012 Jun 28.

Abstract

The precise relationship between GCF2 expression and carcinogenesis has not yet been established. To clarify the metastatic potential of GCF2 in colorectal cancer, HT-29 cells stably suppressing GCF2 expression were injected into the spleens of severe combined immunodeficient (SCID) mice. GCF2 suppression reduced the number of metastatic foci in the liver and reduced fibronectin-induced cell adhesion, migration, and invasion. Downstream from the integrin signaling pathways, GCF2 regulates RhoA interaction with the RGS domain of Leukemia associated RhoGEF (LARG). Altogether, our results suggest that GCF2 plays an important role in colorectal cancer metastasis by regulating RhoA-induced cell adhesion, migration, and invasion.

摘要

GCF2 表达与癌症发生之间的确切关系尚未确定。为了阐明 GCF2 在结直肠癌中的转移潜能,将稳定抑制 GCF2 表达的 HT-29 细胞注入严重联合免疫缺陷(SCID)小鼠的脾脏中。GCF2 的抑制减少了肝转移灶的数量,并减少了纤维连接蛋白诱导的细胞黏附、迁移和侵袭。在整合素信号通路的下游,GCF2 调节 RhoA 与白血病相关 RhoGEF(LARG)的 RGS 结构域的相互作用。总之,我们的结果表明,GCF2 通过调节 RhoA 诱导的细胞黏附、迁移和侵袭在结直肠癌转移中发挥重要作用。

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