Department of Pharmacology, Weifang Medical University, Weifang 261053, P.R. China.
Department of Ophthalmology, Beijing Chaoyang Hospital, Capital Medical University, Beijing 100020, P.R. China.
Mol Med Rep. 2017 Oct;16(4):4577-4582. doi: 10.3892/mmr.2017.7151. Epub 2017 Aug 3.
Uveal melanoma (UM) is characterized by high metastasis and poor prognosis. A more improved understanding of the metastatic mechanism in UM cells is essential for the design of molecular therapy. Grb2‑associated binder 2 (Gab2) has been reported to serve important roles in the progression of various types of human cancer. However, the role of Gab2 in the migration and invasion of UM remains unclear. The present study sought to further assess the expression of Gab2 in UM and the role of Gab2 in the invasion of UM cells. Clinical UM tissue samples and UM cell lines were analyzed using western blot analysis for the expression of Gab2. RNA interference was used to investigate the effect of Gab2 on the migratory and invasive characteristics of UM cells in vitro. The expression levels of matrix metalloproteinase (MMP)2, MMP9 and fascin in Gab2‑knockdown, and control cells were also detected using western blot analysis. A total of 20 clinical UM samples and a subset of UM cell lines were investigated with uniformly high Gab2 expression. In the in vitro experiment, reduction of Gab2 using small interfering RNA inhibited the migration and invasion of UM cells by mediating MMPs, and fascin expression. These data suggest that Gab2 is a useful prognostic marker for UM and a novel therapeutic target for UM metastasis intervention.
葡萄膜黑色素瘤(UM)的特征是转移率高和预后不良。更深入地了解 UM 细胞的转移机制对于设计分子治疗至关重要。Grb2 相关结合蛋白 2(Gab2)已被报道在各种类型的人类癌症的进展中发挥重要作用。然而,Gab2 在 UM 的迁移和侵袭中的作用尚不清楚。本研究旨在进一步评估 Gab2 在 UM 中的表达及其在 UM 细胞侵袭中的作用。使用 Western blot 分析分析临床 UM 组织样本和 UM 细胞系中 Gab2 的表达。使用 RNA 干扰研究 Gab2 对 UM 细胞体外迁移和侵袭特性的影响。使用 Western blot 分析还检测了 Gab2 敲低和对照细胞中基质金属蛋白酶(MMP)2、MMP9 和 fascin 的表达水平。共对 20 例临床 UM 样本和一部分 UM 细胞系进行了研究,结果均显示 Gab2 表达水平较高。在体外实验中,使用小干扰 RNA 降低 Gab2 可通过调节 MMPs 和 fascin 表达来抑制 UM 细胞的迁移和侵袭。这些数据表明,Gab2 是 UM 的一个有用的预后标志物,也是 UM 转移干预的一个新的治疗靶点。