Girdin, an actin-binding protein, is critical for migration, adhesion, and invasion of human glioblastoma cells.

Abstract

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.

• Authors: Feng Gu, Li Wang, Jia He, Xiaoli Liu, Huikun Zhang, Wenliang Li, Li Fu, Yongjie Ma
• Journal: Journal of neurochemistry (J Neurochem) Vol. 131 Issue 4 Pg. 457-69 (Nov 2014) ISSN: 1471-4159 [Electronic] England
• PMID: 25060559 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2014 International Society for Neurochemistry.

Chemical References

• CCDC88A protein, human
• Chemokines
• Microfilament Proteins
• Vesicular Transport Proteins
• MMP2 protein, human
• Matrix Metalloproteinase 2

Topics

• Animals
• Brain Neoplasms (metabolism, pathology)
• Cell Adhesion (drug effects, physiology)
• Cell Line, Tumor
• Cell Movement (drug effects, physiology)
• Cell Proliferation (physiology)
• Chemokines (metabolism)
• Chemotaxis (drug effects, genetics)
• Female
• Gene Expression Regulation, Neoplastic (physiology)
• Glioblastoma (metabolism, pathology)
• Humans
• Male
• Matrix Metalloproteinase 2 (metabolism)
• Mice
• Mice, Nude
• Microfilament Proteins (genetics, metabolism)
• Neoplasm Invasiveness (physiopathology)
• Vesicular Transport Proteins (genetics, metabolism)
• Wounds and Injuries (metabolism, pathology)