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Abstract：
Tumor necrosis factor receptor superfamily member 11B (TNFRSF11B) has been studied to be involved in the development and progression of several human malignancies. However, little is unveiled regarding the complex mechanisms of TNFRSF11B in human gastric cancer (GC). The clinical significance of TNFRSF11B was assessed in 70 and 160 GC tissues using immunohistochemistry method and gene microarray analysis, respectively. The biological function of TNFRSF11B was studied in vitro and in vivo assays. Immunofluorescence assay was used to evaluate the expression of β-catenin in the nucleus. The expression of β-catenin and related protein was determined by Western blot. The interaction between TNFRSF11B and GSK3β was detected by co-immunoprecipitation. We demonstrated that TNFRSF11B was highly expressed in the cytoplasm of GC and associated with the patient poor outcome. Our studies showed that TNFRSF11B in GC cells significantly promoted cell proliferation, migration, invasion in vitro and tumorigenic ability in vitro and in vivo. Meanwhile, TNFRSF11B inhibited GC cell apoptosis. The proportion of nuclear active β-catenin showed positively correlation with TNFRSF11B expression. TNFRSF11B directly combined with GSK-3β upregulating its phosphorylation, and increased expression of β-catenin and its downstream effectors. Collectively, these findings demonstrate that TNFRSF11B promote the aggressive phenotypes of GC cells and activated Wnt/β-catenin signaling. Accordingly, TNFRSF11B had potential as a biomarker and inhibition of TNFRSF11B expression might offer a new therapeutic target for GC patients.
摘要：
已经研究了肿瘤坏死因子受体超家族成员11B（TNFRSF11B）与几种人类恶性肿瘤的发生和发展有关。然而,关于TNFRSF11B在人胃癌（GC）中的复杂机制，鲜为人知。采用免疫组织化学方法和基因芯片分析在70和160例GC组织中评估TNFRSF11B的临床意义,分别。在体外和体内试验中研究了TNFRSF11B的生物学功能。免疫荧光法检测β-catenin在细胞核中的表达。Westernblot检测β-catenin及相关蛋白的表达。免疫共沉淀法检测TNFRSF11B与GSK3β的相互作用。我们证明TNFRSF11B在GC的细胞质中高表达，并与患者不良预后有关。我们的研究表明，TNFRSF11B在GC细胞中显著促进细胞增殖，迁移,体外侵袭和体外和体内致瘤能力。同时,TNFRSF11B抑制GC细胞凋亡。核活性β-catenin比例与TNFRSF11B表达呈正相关。TNFRSF11B直接结合GSK-3β上调其磷酸化，β-连环蛋白及其下游效应子的表达增加。总的来说，这些发现表明TNFRSF11B促进GC细胞的侵袭性表型并激活Wnt/β-catenin信号传导。因此，TNFRSF11B具有作为生物标志物的潜力，抑制TNFRSF11B的表达可能为GC患者提供新的治疗靶点。
