title: Glucocorticoid Receptor β Acts as a Co-activator of T-Cell Factor 4 and Enhances Glioma Cell Proliferation.
abstract: 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.
authors.affiliation: Department of Clinical Laboratory Science, Wuxi People's Hospital Affiliated to Nanjing Medical University, Wuxi, 214023, People's Republic of China.|Wuxi Institute of Translational Medicine, Wuxi, 214023, People's Republic of China.|Jiangsu Key laboratory of Organ Transplantation, Wuxi, 214023, People's Republic of China.
authors.forename: Qian
authors.initials: Q
authors.lastname: Wang
authors.affiliation: Wuxi Institute of Translational Medicine, Wuxi, 214023, People's Republic of China.|Jiangsu Key laboratory of Organ Transplantation, Wuxi, 214023, People's Republic of China.|Department of Medical Oncology, Wuxi People's Hospital Affiliated to Nanjing Medical University, Wuxi, 214023, People's Republic of China.
authors.forename: Pei-Hua
authors.initials: PH
authors.lastname: Lu
authors.affiliation: Department of Neurosurgery, Huashan Hospital, Fudan University, Shanghai, 200040, People's Republic of China.
authors.forename: Zhi-Feng
authors.initials: ZF
authors.lastname: Shi
authors.affiliation: Molecular Biology & Protein Engineering, XBio, Inc., Shanghai, 201318, People's Republic of China.
authors.forename: Yan-Juan
authors.initials: YJ
authors.lastname: Xu
authors.affiliation: Wuxi Institute of Translational Medicine, Wuxi, 214023, People's Republic of China.|Jiangsu Key laboratory of Organ Transplantation, Wuxi, 214023, People's Republic of China.
authors.forename: Jie
authors.initials: J
authors.lastname: Xiang
authors.affiliation: Training Center of Basic Medical Experiments, School of Medicine, Shanghai Jiaotong University, Shanghai, 200025, People's Republic of China.
authors.forename: Yan-Xia
authors.initials: YX
authors.lastname: Wang
authors.affiliation: Department of Anatomy and Cell Biology, Indiana University School of Medicine, Indianapolis, IN, 46202, USA.|Spinal Cord and Brain Injury Research Group, Stark Neurosciences Research Institute, Indiana University School of Medicine, Indianapolis, IN, 46202, USA.
authors.forename: Ling-Xiao
authors.initials: LX
authors.lastname: Deng
authors.affiliation: Department of Clinical Laboratory Science, Wuxi People's Hospital Affiliated to Nanjing Medical University, Wuxi, 214023, People's Republic of China.|Wuxi Institute of Translational Medicine, Wuxi, 214023, People's Republic of China.|Jiangsu Key laboratory of Organ Transplantation, Wuxi, 214023, People's Republic of China.
authors.forename: Ping
authors.initials: P
authors.lastname: Xie
authors.affiliation: Department of Clinical Laboratory Science, Wuxi People's Hospital Affiliated to Nanjing Medical University, Wuxi, 214023, People's Republic of China.|Wuxi Institute of Translational Medicine, Wuxi, 214023, People's Republic of China.|Jiangsu Key laboratory of Organ Transplantation, Wuxi, 214023, People's Republic of China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Yin
authors.affiliation: Department of Clinical Laboratory Science, Wuxi People's Hospital Affiliated to Nanjing Medical University, Wuxi, 214023, People's Republic of China.|Wuxi Institute of Translational Medicine, Wuxi, 214023, People's Republic of China.|Jiangsu Key laboratory of Organ Transplantation, Wuxi, 214023, People's Republic of China.
authors.forename: Bin
authors.initials: B
authors.lastname: Zhang
authors.affiliation: Department of Clinical Laboratory Science, Wuxi People's Hospital Affiliated to Nanjing Medical University, Wuxi, 214023, People's Republic of China.|Wuxi Institute of Translational Medicine, Wuxi, 214023, People's Republic of China.|Jiangsu Key laboratory of Organ Transplantation, Wuxi, 214023, People's Republic of China.
authors.forename: Hui-Jun
authors.initials: HJ
authors.lastname: Mu
authors.affiliation: Department of Clinical Laboratory Science, Wuxi People's Hospital Affiliated to Nanjing Medical University, Wuxi, 214023, People's Republic of China.|Wuxi Institute of Translational Medicine, Wuxi, 214023, People's Republic of China.|Jiangsu Key laboratory of Organ Transplantation, Wuxi, 214023, People's Republic of China.
authors.forename: Wei-Zhen
authors.initials: WZ
authors.lastname: Qiao
authors.affiliation: Department of Neurosurgery, Renji Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, 200127, People's Republic of China.
authors.forename: Hua
authors.initials: H
authors.lastname: Cui
authors.affiliation: Department of Clinical Laboratory Science, Wuxi People's Hospital Affiliated to Nanjing Medical University, Wuxi, 214023, People's Republic of China. zoujan@gmail.com.|Wuxi Institute of Translational Medicine, Wuxi, 214023, People's Republic of China. zoujan@gmail.com.|Jiangsu Key laboratory of Organ Transplantation, Wuxi, 214023, People's Republic of China. zoujan@gmail.com.
authors.forename: Jian
authors.initials: J
authors.lastname: Zou
mesh_terms: D000818:Animals; D001943:Breast Neoplasms / Q000473:pathology; D019556:COS Cells; D002455:Cell Division; D045744:Cell Line, Tumor; D002522:Chlorocebus aethiops; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D005910:Glioma / Q000473:pathology*; D057809:HEK293 Cells; D064593:Heterografts; D006801:Humans; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009363:Neoplasm Proteins / Q000378:metabolism*; D009368:Neoplasm Transplantation; D025941:Protein Interaction Mapping; D017434:Protein Structure, Tertiary; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000235:genetics; D011965:Receptors, Glucocorticoid / Q000378:metabolism*; D058118:Transcription Factor 7-Like 2 Protein / Q000235:genetics / Q000378:metabolism*; D014162:Transfection; D014410:Tumor Stem Cell Assay; D060449:Wnt Signaling Pathway / Q000502:physiology*
chemical_list: D009363:Neoplasm Proteins; D034741:RNA, Small Interfering; D011965:Receptors, Glucocorticoid; D058118:Transcription Factor 7-Like 2 Protein; C121943:glucocorticoid receptor beta
keywords: Glioma; Glucocorticoid receptor β; Interact; Proliferation; TCF-4; TCF/LEF