The Overexpression of IQGAP1 and β-Catenin Is Associated with Tumor Progression in Hepatocellular Carcinoma In Vitro and In Vivo.
The Overexpression of IQGAP1 and β-Catenin Is Associated with Tumor Progression in Hepatocellular Carcinoma In Vitro and In Vivo.
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IQGAP1和β-Catenin的过度表达与体外和体内肝细胞癌的肿瘤进展相关
DOI：
10.1371/journal.pone.0133770
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发表时间：
2015
期刊：
影响因子：
3.7
通讯作者：
Liang S
中科院分区：
文献类型：
--
作者：
Jin X;Liu Y;Liu J;Lu W;Liang Z;Zhang D;Liu G;Zhu H;Xu N;Liang S
iq结构域gtpase激活蛋白1 （IQGAP1）是一种多功能支架蛋白，可与多种蛋白相互作用，调控细胞粘附和细胞迁移。IQGAP1的异常表达广泛存在于多种癌症中，但其与相互作用蛋白合作参与肿瘤发生的生物学作用尚不清楚。在本研究中，我们发现IQGAP1与β-catenin相互作用，调节肝细胞癌（HCC）细胞中β-catenin的表达。在几种HCC细胞系中，IQGAP1和β-catenin的表达水平及其相关性与细胞转移能力呈正相关。上调IQGAP1和β-catenin可提高HCC细胞的增殖和迁移能力，而通过小干扰RNA敲低IQGAP1可降低β-catenin的表达，导致细胞体外增殖和迁移能力降低。此外，IQGAP1和β-catenin在人HCC组织中通常也存在显著的高表达，特别是其过表达与肿瘤恶性有临床病理相关性。一般来说，IQGAP1和β-catenin的过表达和相互作用通过促进细胞增殖和迁移来促进HCC的进展。
The IQ-domain GTPase-activating protein 1 (IQGAP1) is a multifunctional scaffold protein, which interacts with diverse proteins to regulate cell adhesion and cell migration. The abnormal expression of IQGAP1 widely exists in many cancers, but biological roles of IQGAP1 cooperation with its interacting proteins to involve in tumorigenesis remain to clarify. In this study, we have found that IQGAP1 interacts with β-catenin and regulates β-catenin expression in hepatocellular carcinoma (HCC) cells. The expression levels of IQGAP1 and β-catenin and their associations have a positive correlation with cell metastasis ability in several HCC cell lines. The up-regulation of IQGAP1 and β-catenin improves cell proliferation and migration ability of HCC cells, whereas the knockdown of IQGAP1 by small interfering RNA can decrease β-catenin expression, which results in the reduction of cell proliferation and migration ability in vitro. In addition, a significantly higher expression of IQGAP1 and β-catenin also usually exists in human HCC tissues, especially their overexpression is clinicopathologically associated with tumor malignancy. Generally the overexpression and interactions of IQGAP1 and β-catenin contribute to HCC progression by promoting cell proliferation and migration.