title: TCTP promotes glioma cell proliferation in vitro and in vivo via enhanced β-catenin/TCF-4 transcription.
abstract: Background The translationally controlled tumor protein (TCTP) is a multifunctional protein that plays important roles in immune responses, cell proliferation, tumorigenicity and cell apoptosis. Here, we examined the clinical value of TCTP in glioma patient survival and investigated the functional roles and mechanism of TCTP in glioma development. Methods TCTP expression was determined through immunohistochemical staining, immunoblotting, and quantitative real-time PCR (qRT-PCR). TCTP or TCF-4 expression was silenced using short hairpin (sh) RNA. In vitro cell proliferation was detected using MTT, BrdU and colony formation assays, and in vivo tumor growth was performed using the xenograft model. TCTP/TCF-4/β-catenin association was detected using a co-immunoprecipitation (co-IP) assay. TCF-4 transcription activity was detected using a TOPflash/FOPflash report gene assay. Wnt/β-catenin-targeted gene expression was detected through Western blotting. Results TCTP protein levels were significantly elevated in high-grade gliomas compared with low-grade gliomas and normal brain tissues. Importantly, the expression of TCTP was significantly associated with poorer overall survival and disease-free survival, and TCTP also reduced the survival rate after treatment with radiotherapy and temozolomide (RT-TMZ) for glioma patients. The ectopic expression of TCTP enhanced glioma cell proliferation both in vitro and in vivo, whereas the knockdown of TCTP inhibited this effect. Similarly, the overexpression of TCTP increased β-catenin binding to TCF-4, TOPflash report gene transcription activity, and the expression of Wnt/β-catenin signaling target genes including c-Myc and cyclin D1; notably, the knockdown of TCTP reduced these effects. The knockdown of TCF-4 using shRNA rescued the enhanced cell proliferation induced by the overexpression of TCTP. Conclusion TCTP is associated with reduced survival of glioma patients and induces glioma tumor growth through enhanced Wnt/β-catenin signaling.
authors: Corresponding authors: Keshen Li, MD, PhD, Institute of Neurology, Guangdong Medical College, Zhanjiang 524001, China. zhaozhaozhao2012@gmail.com); Bin Zhao, MD, PhD, Guangdong Key Laboratory of Age-Related Cardiac and Cerebral Diseases, Affiliated Hospital of Guangdong Medical College, Zhanjiang 524001, China (zhaobine@vip.tom.com.
authors: Xuefeng
authors: X
authors: Gu
authors: Lifen
authors: L
authors: Yao
authors: Guoda
authors: G
authors: Ma
authors: Lili
authors: L
authors: Cui
authors: You
authors: Y
authors: Li
authors: Wandong
authors: W
authors: Liang
authors: Bin
authors: B
authors: Zhao
authors: Keshen
authors: K
authors: Li
mesh_terms: D000818:Animals; D017209:Apoptosis; D051778:Basic Helix-Loop-Helix Leucine Zipper Transcription Factors / Q000235:genetics* / Q000378:metabolism; D014408:Biomarkers, Tumor / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D015153:Blotting, Western; D049109:Cell Proliferation; D015972:Gene Expression Regulation, Neoplastic; D005910:Glioma / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D006801:Humans; D007124:Immunoenzyme Techniques; D066298:In Vitro Techniques; D051379:Mice; D008819:Mice, Nude; D012333:RNA, Messenger / Q000235:genetics; D034741:RNA, Small Interfering / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D000073940:Transcription Factor 4; D014157:Transcription Factors / Q000235:genetics* / Q000378:metabolism; D014158:Transcription, Genetic; D014407:Tumor Cells, Cultured; D000090324:Tumor Protein, Translationally-Controlled 1; D023041:Xenograft Model Antitumor Assays; D051176:beta Catenin / Q000235:genetics* / Q000378:metabolism
chemical_list: D051778:Basic Helix-Loop-Helix Leucine Zipper Transcription Factors; D014408:Biomarkers, Tumor; D012333:RNA, Messenger; D034741:RNA, Small Interfering; C532096:TCF4 protein, human; C000715647:TPT1 protein, human; C000715648:Tpt1 protein, mouse; D000073940:Transcription Factor 4; D014157:Transcription Factors; D000090324:Tumor Protein, Translationally-Controlled 1; D051176:beta Catenin
keywords: TCF-4; TCTP; glioma; β-catenin