1. Knockdown of FRAT1 expression by RNA interference inhibits human glioblastoma cell growth, migration and invasion.
- Author
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Guo G, Kuai D, Cai S, Xue N, Liu Y, Hao J, Fan Y, Jin J, Mao X, Liu B, Zhong C, Zhang X, Yue Y, Liu X, Ma N, and Guo Y
- Subjects
- Adaptor Proteins, Signal Transducing, Animals, Cell Cycle genetics, Cell Line, Tumor, Cell Proliferation, Cell Transformation, Neoplastic pathology, Down-Regulation genetics, Gene Expression Regulation, Neoplastic, Humans, Intracellular Signaling Peptides and Proteins genetics, Intracellular Signaling Peptides and Proteins metabolism, Mice, Mice, Nude, Neoplasm Invasiveness, Proto-Oncogene Mas, Proto-Oncogene Proteins genetics, Proto-Oncogene Proteins metabolism, RNA, Messenger genetics, RNA, Messenger metabolism, Tumor Stem Cell Assay, Xenograft Model Antitumor Assays, Cell Movement genetics, Gene Knockdown Techniques, Glioblastoma genetics, Glioblastoma pathology, RNA Interference
- Abstract
Background: FRAT1 positively regulates the Wnt/β-catenin signaling pathway by inhibiting GSK-3-mediated phosphorylation of β-catenin. It was originally characterized as a protein frequently rearranged in advanced T cell lymphoma, but has recently also been identified as a proto-oncogene involved in tumorigenesis. Our previous studies showed that FRAT1 was dramatically overexpressed in gliomas and its expression level was significantly increased along with clinicopathological grades., Methods: In the current study, we used RT-PCR and Western blotting to assess the mRNA and protein levels of FRAT1 in three glioma cell lines. In addition, to evaluate its functional role in gliomas, we examined the effects of FRAT1 knockdown on proliferation, migration and invasion in vitro and tumor growth in vivo using glioblastoma U251 cells and RNAi., Results: FRAT1 was highly expressed in all three glioma cell lines. RNAi-mediated down-regulation of endogenous FRAT1 in human glioblastoma U251 cells resulted in suppression of cell proliferation, arrest of cell cycle, inhibition of cell migration and invasion in vitro. Moreover, FRAT1 depletion significantly impaired tumor xenograft growth in nude mice., Conclusions: Our results highlight the potential role of FRAT1 in tumorigenesis and progression of glioblastoma. These findings provide a biological basis for FRAT1 as a potential molecular marker for improved pathological grading and as a novel candidate therapeutic target for glioblastoma management.
- Published
- 2013
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