title: Knockdown of FRAT1 expression by RNA interference inhibits human glioblastoma cell growth, migration and invasion.
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.
authors.affiliation: Department of Neurosurgery, The First Hospital, Shanxi Medical University, Taiyuan, Shanxi Province, People's Republic of China.
authors.forename: Geng
authors.initials: G
authors.lastname: Guo
authors.forename: Dong
authors.initials: D
authors.lastname: Kuai
authors.forename: Sang
authors.initials: S
authors.lastname: Cai
authors.forename: Naizhao
authors.initials: N
authors.lastname: Xue
authors.forename: Yueting
authors.initials: Y
authors.lastname: Liu
authors.forename: Jiehe
authors.initials: J
authors.lastname: Hao
authors.forename: Yimin
authors.initials: Y
authors.lastname: Fan
authors.forename: Ji
authors.initials: J
authors.lastname: Jin
authors.forename: Xinggang
authors.initials: X
authors.lastname: Mao
authors.forename: Bolin
authors.initials: B
authors.lastname: Liu
authors.forename: Chengliang
authors.initials: C
authors.lastname: Zhong
authors.forename: Xiang
authors.initials: X
authors.lastname: Zhang
authors.forename: Yi
authors.initials: Y
authors.lastname: Yue
authors.forename: Xiaodong
authors.initials: X
authors.lastname: Liu
authors.forename: Ning
authors.initials: N
authors.lastname: Ma
authors.forename: Yuhong
authors.initials: Y
authors.lastname: Guo
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D000818:Animals; D002453:Cell Cycle / Q000235:genetics; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics*; D049109:Cell Proliferation; D002471:Cell Transformation, Neoplastic / Q000473:pathology; D015536:Down-Regulation / Q000235:genetics; D015972:Gene Expression Regulation, Neoplastic; D055785:Gene Knockdown Techniques; D005909:Glioblastoma / Q000235:genetics* / Q000473:pathology*; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008819:Mice, Nude; D009361:Neoplasm Invasiveness; D000090063:Proto-Oncogene Mas; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000378:metabolism; D034622:RNA Interference; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D014410:Tumor Stem Cell Assay; D023041:Xenograft Model Antitumor Assays
chemical_list: D048868:Adaptor Proteins, Signal Transducing; C491819:FRAT1 protein, human; D047908:Intracellular Signaling Peptides and Proteins; C000715470:MAS1 protein, human; D000090063:Proto-Oncogene Mas; D011518:Proto-Oncogene Proteins; D012333:RNA, Messenger