Grb2-associated binder 2 expression and its roles in uveal melanoma invasion

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.