Browsing by Author "Mu, Hui-Jun"

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    Glucocorticoid Receptor β Acts As a Co-activator of T-Cell Factor 4 and Enhances Glioma Cell Proliferation
    (Springer, 2015-12) Wang, Qian; Lu, Pei-Hua; Shi, Zhi-Feng; Xu, Yan-Juan; Xiang, Jie; Wang, Yan-Xia; Deng, Ling-Xiao; Xie, Ping; Yin, Ying; Zhang, Bin; Mu, Hui-Jun; Qiao, Wei-Zhen; Cui, Hua; Zou, Jian; Department of Neurological Surgery, IU School of Medicine
    We previously reported that glucocorticoid receptor β (GRβ) regulates injury-mediated astrocyte activation and contributes to glioma pathogenesis via modulation of β-catenin/T-cell factor/lymphoid enhancer factor (TCF/LEF) transcriptional activity. The aim of this study was to characterize the mechanism behind cross-talk between GRβ and β-catenin/TCF in the progression of glioma. Here, we reported that GRβ knockdown reduced U118 and Shg44 glioma cell proliferation in vitro and in vivo. Mechanistically, we found that GRβ knockdown decreased TCF/LEF transcriptional activity without affecting β-catenin/TCF complex. Both GRα and GRβ directly interact with TCF-4, while only GRβ is required for sustaining TCF/LEF activity under hormone-free condition. GRβ bound to the N-terminus domain of TCF-4 its influence on Wnt signaling required both ligand- and DNA-binding domains (LBD and DBD, respectively). GRβ and TCF-4 interaction is enough to maintain the TCF/LEF activity at a high level in the absence of β-catenin stabilization. Taken together, these results suggest a novel cross-talk between GRβ and TCF-4 which regulates Wnt signaling and the proliferation in gliomas.