Girdin, an
actin-binding protein, possesses versatile functions in a multitude of cellular processes. Although several studies have shown that Girdin is involved in the cell
DNA synthesis, actin cytoskeleton rearrangement, and cell motility, the molecular mechanisms of Girdin in
tumor development and progression remain elusive. In this study, through over-expression and
siRNA experiments, we found that Girdin increased migration of LN229 human
glioblastoma cells. On the other hand, reducing Girdin impaired
F-actin polymerization, which is essential for cell morphogenesis and motility.
Matrix metalloproteinase 2, critical in human
glioma migration and invasion, was down-regulated upon Girdin reduction and led to decreased invasion in vitro and in vivo. In addition, silencing Girdin expression impaired the phosphorylation of two important adhesion molecules,
integrin β1 and
focal adhesion kinase, resulting in cell adhesion defects. Our immunohistochemical study on human
gliomas tissue sections indicated that Girdin expression was positively related with
glioma malignancy, supporting the in vitro and in vivo results from cell lines. Collectively, our findings suggest a critical role for Girdin in
glioma infiltration. We show that reduction of Girdin, an
actin-binding protein, leads to impaired
F-actin polymerization and down-regulated expression of matrix
metallopeptidase protein 2 (MMP-2), phosphorylated
integrin β1, and phosphorylated
focal adhesion kinase (FAK), which resulted in decreased migration, adhesion, and invasion of
glioblastoma cells. Girdin was positively correlated with
glioma malignancy and negatively associated with clinical prognosis, suggesting Girdin as a critical regulator in
glioma infiltration.