Premium
Girdin, an actin‐binding protein, is critical for migration, adhesion, and invasion of human glioblastoma cells
Author(s) -
Gu Feng,
Wang Li,
He Jia,
Liu Xiaoli,
Zhang Huikun,
Li Wenliang,
Fu Li,
Ma Yongjie
Publication year - 2014
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/jnc.12831
Subject(s) - microbiology and biotechnology , focal adhesion , biology , cell migration , integrin , actin cytoskeleton , cancer research , cell adhesion molecule , cell adhesion , glioma , cytoskeleton , phosphorylation , cell , biochemistry
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.