title: 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: Key Laboratory of Cancer Prevention and Therapy of Tianjin, National Clinical Research Center of Cancer, Tianjin Medical University Cancer Institute and Hospital, Tianjin, China.
authors: Feng
authors: F
authors: Gu
authors: Li
authors: L
authors: Wang
authors: Jia
authors: J
authors: He
authors: Xiaoli
authors: X
authors: Liu
authors: Huikun
authors: H
authors: Zhang
authors: Wenliang
authors: W
authors: Li
authors: Li
authors: L
authors: Fu
authors: Yongjie
authors: Y
authors: Ma
mesh_terms: D000818:Animals; D001932:Brain Neoplasms / Q000378:metabolism / Q000473:pathology; D002448:Cell Adhesion / Q000187:drug effects / Q000502:physiology*; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects / Q000502:physiology*; D049109:Cell Proliferation / Q000502:physiology; D018925:Chemokines / Q000378:metabolism; D002633:Chemotaxis / Q000187:drug effects / Q000235:genetics; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000502:physiology; D005909:Glioblastoma / Q000378:metabolism / Q000473:pathology; D006801:Humans; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism; D051379:Mice; D008819:Mice, Nude; D008840:Microfilament Proteins / Q000235:genetics / Q000378:metabolism*; D009361:Neoplasm Invasiveness / Q000503:physiopathology*; D033921:Vesicular Transport Proteins / Q000235:genetics / Q000378:metabolism*; D014947:Wounds and Injuries / Q000378:metabolism / Q000473:pathology
chemical_list: C502451:CCDC88A protein, human; D018925:Chemokines; D008840:Microfilament Proteins; D033921:Vesicular Transport Proteins; C522361:MMP2 protein, human; D020778:Matrix Metalloproteinase 2
keywords: Girdin; adhesion; glioblastoma; invasion; matrix metalloproteinase; migration