title: SOX4 inhibits GBM cell growth and induces G0/G1 cell cycle arrest through Akt-p53 axis.
abstract: BACKGROUND
  SOX4 is a transcription factor required for tissue development and differentiation in vertebrates. Overexpression of SOX4 has been reported in many cancers including glioblastoma multiforme (GBM), however, the underlying mechanism of actions has not been studied. In this study, we investigated the role of SOX4 in GBM.
  
  
  METHODS
  Kaplan-Meier analysis was performed to assess the association between SOX4 expression levels and survival times in primary GBM samples. Cre/lox P system was used to generate gain or loss of SOX4 in GBM cells, and microarray analysis uncovered the regulation network of SOX4 in GBM cells.
  
  
  RESULTS
  High SOX4 expression was significantly associated with good prognosis of primary GBMs. SOX4 inhibited the growth of GBM cell line LN229, A172G and U87MG, partly via the activation of p53-p21 signaling and down-regulation of phosphorylated AKT1. Gene expression profiling and subsequent gene ontology analysis showed that SOX4 influenced several key pathways including the Wnt/ beta-catenin and TGF-beta signaling pathways.
  
  
  CONCLUSIONS
  Our study found that SOX4 acts as a tumor suppressor in GBM cells by induce cell cycle arrest and inhibiting cell growth.
authors.affiliation: Cancer Institute (Key Laboratory of Cancer Prevention and Intervention, China National Ministry of Education), Second Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, Zhejiang Province, P R China. jingzh1985@gmail.com.|Systems Biology Division and Propriumbio Research Center, Zhejiang-California International Nanosystems Institute (ZCNI), Zhejiang University, Hangzhou, Zhejiang Province, P R China. jingzh1985@gmail.com.
authors.forename: Jing
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Cancer Institute (Key Laboratory of Cancer Prevention and Intervention, China National Ministry of Education), Second Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, Zhejiang Province, P R China. jianghuawei411@163.com.|Systems Biology Division and Propriumbio Research Center, Zhejiang-California International Nanosystems Institute (ZCNI), Zhejiang University, Hangzhou, Zhejiang Province, P R China. jianghuawei411@163.com.
authors.forename: Huawei
authors.initials: H
authors.lastname: Jiang
authors.affiliation: Department of Bioinformatics, School of Basic Medical Sciences, Nanjing Medical University, Nanjing, Jiangsu Province, P R China. dreambetter@gmail.com.
authors.forename: Jiaofang
authors.initials: J
authors.lastname: Shao
authors.affiliation: Systems Biology Division and Propriumbio Research Center, Zhejiang-California International Nanosystems Institute (ZCNI), Zhejiang University, Hangzhou, Zhejiang Province, P R China. daianna-861103@163.com.
authors.forename: Ruifang
authors.initials: R
authors.lastname: Mao
authors.affiliation: Systems Biology Division and Propriumbio Research Center, Zhejiang-California International Nanosystems Institute (ZCNI), Zhejiang University, Hangzhou, Zhejiang Province, P R China. liujie_1914@163.com.
authors.forename: Jie
authors.initials: J
authors.lastname: Liu
authors.affiliation: Systems Biology Division and Propriumbio Research Center, Zhejiang-California International Nanosystems Institute (ZCNI), Zhejiang University, Hangzhou, Zhejiang Province, P R China. mychch@126.com.
authors.forename: Yingying
authors.initials: Y
authors.lastname: Ma
authors.affiliation: Cancer Institute (Key Laboratory of Cancer Prevention and Intervention, China National Ministry of Education), Second Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, Zhejiang Province, P R China. xffangnj@gmail.com.
authors.forename: Xuefeng
authors.initials: X
authors.lastname: Fang
authors.affiliation: Systems Biology Division and Propriumbio Research Center, Zhejiang-California International Nanosystems Institute (ZCNI), Zhejiang University, Hangzhou, Zhejiang Province, P R China. coco.206@gmail.com.
authors.forename: Na
authors.initials: N
authors.lastname: Zhao
authors.affiliation: Cancer Institute (Key Laboratory of Cancer Prevention and Intervention, China National Ministry of Education), Second Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, Zhejiang Province, P R China. zhengshu@zju.edu.cn.
authors.forename: Shu
authors.initials: S
authors.lastname: Zheng
authors.affiliation: Cancer Institute (Key Laboratory of Cancer Prevention and Intervention, China National Ministry of Education), Second Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, Zhejiang Province, P R China. Biaoylin@gmail.com.|Systems Biology Division and Propriumbio Research Center, Zhejiang-California International Nanosystems Institute (ZCNI), Zhejiang University, Hangzhou, Zhejiang Province, P R China. Biaoylin@gmail.com.|Department of Urology, University of Washington, Seattle, WA, 98195, USA. Biaoylin@gmail.com.
authors.forename: Biaoyang
authors.initials: B
authors.lastname: Lin
mesh_terms: D045744:Cell Line, Tumor; D049109:Cell Proliferation; D015536:Down-Regulation; D059585:G1 Phase Cell Cycle Checkpoints / Q000502:physiology; D005909:Glioblastoma / Q000235:genetics / Q000473:pathology*; D006801:Humans; D053208:Kaplan-Meier Estimate; D055751:SOXC Transcription Factors / Q000235:genetics*; D015398:Signal Transduction
chemical_list: C083431:SOX4 protein, human; D055751:SOXC Transcription Factors