1. SOX4 inhibits GBM cell growth and induces G0/G1 cell cycle arrest through Akt-p53 axis
- Author
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Jie Liu, Yingying Ma, Na Zhao, Biaoyang Lin, Huawei Jiang, Ruifang Mao, Jiaofang Shao, Jing Zhang, Xuefeng Fang, and Shu Zheng
- Subjects
Cell cycle checkpoint ,Clinical Neurology ,Down-Regulation ,Kaplan-Meier Estimate ,SOXC Transcription Factors ,SOX4 ,Cell Line, Tumor ,Medicine ,Humans ,Protein kinase B ,Cell Proliferation ,Microarray analysis techniques ,Cell growth ,business.industry ,Wnt signaling pathway ,General Medicine ,G1 Phase Cell Cycle Checkpoints ,nervous system diseases ,Gene expression profiling ,Cancer research ,Neurology (clinical) ,Signal transduction ,business ,Glioblastoma ,Neuroscience ,Signal Transduction ,Research Article - 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. Electronic supplementary material The online version of this article (doi:10.1186/s12883-014-0207-y) contains supplementary material, which is available to authorized users.
- Published
- 2014