title: Gab2 expression in glioma and its implications for tumor invasion.
abstract: Gliomas are characterized by high invasiveness and poor prognosis. Better understanding of the mechanism of invasion in glioma cells is essential to the design of effective therapy. Recently Grb2-associated binder 2 (Gab2), a member of the DOS/Gab family of scaffolding adapters, has been reported to play important roles in the development and progression of human cancers. However, it is not known whether Gab2 has any role in the migration and invasion of gliomas. This study attempts to investigate the association between Gab2 expression and progression of gliomas and the molecular mechanism of Gab2 in the glioma cell invasion. Methods. The expression of Gab2 in pairs of matched glioma tissues and their normal brain tissues was detected by Western blot. Immunohistochemistry was applied to evaluate the expression of Gab2 in 163 cases of histologically diagnosed gliomas. The invasive character of Gab2 decreased glioma cells and control glioma cells were investigated in vitro and in vivo in SCID mice brain. Results. Gab2 is found to be high expressed in gliomas and a subset of cancer cell lines. Statistical analysis suggested that the up-regulation of Gab2 correlated with the WHO grade of gliomas (p < 0.01) and that patients with high Gab2 expression levels exhibited shorter survival time (p < 0.01). In an animal experiment, knockdown of Gab2 through siRNA inhibited invasive ability of glioma cells into the brain of SCID mice. In cell research, reduction of Gab2 by siRNA inhibits the migration and invasion of glioma cells by mediating cytoskeleton rearrangement and MMPs expression. Additionally, IGF-1-induced pAkt and pmTOR phosphorylation was suppressed by the knockdown of Gab2. Conclusion. Gab2 may be a useful prognostic marker for gliomas and a novel therapeutic target for glioma invasion intervention.
authors.affiliation: Department of Oncology, Nanfang Hospital of Southern Medical University , Guangzhou , PR China.
authors.forename: Lihong
authors.initials: L
authors.lastname: Shi
authors.forename: Xiuning
authors.initials: X
authors.lastname: Sun
authors.forename: Jin
authors.initials: J
authors.lastname: Zhang
authors.forename: Chunling
authors.initials: C
authors.lastname: Zhao
authors.forename: Hongli
authors.initials: H
authors.lastname: Li
authors.forename: Zhijun
authors.initials: Z
authors.lastname: Liu
authors.forename: Chunyan
authors.initials: C
authors.lastname: Fang
authors.forename: Xuejian
authors.initials: X
authors.lastname: Wang
authors.forename: Chunzhen
authors.initials: C
authors.lastname: Zhao
authors.forename: Xiurong
authors.initials: X
authors.lastname: Zhang
authors.forename: Fenghua
authors.initials: F
authors.lastname: Zhou
authors.forename: Shijun
authors.initials: S
authors.lastname: Lu
authors.forename: Rongcheng
authors.initials: R
authors.lastname: Luo
authors.forename: Baogang
authors.initials: B
authors.lastname: Zhang
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000818:Animals; D015153:Blotting, Western; D001932:Brain Neoplasms / Q000378:metabolism / Q000473:pathology; D016022:Case-Control Studies; D002448:Cell Adhesion; D002465:Cell Movement; D049109:Cell Proliferation; D002633:Chemotaxis; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005910:Glioma / Q000378:metabolism* / Q000473:pathology*; D006801:Humans; D007124:Immunoenzyme Techniques; D008297:Male; D051379:Mice; D016513:Mice, SCID; D008875:Middle Aged; D060787:Neoplasm Grading; D009361:Neoplasm Invasiveness; D034741:RNA, Small Interfering / Q000235:genetics; D014407:Tumor Cells, Cultured
chemical_list: D048868:Adaptor Proteins, Signal Transducing; C490895:GAB2 protein, human; D034741:RNA, Small Interfering