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经典 WNT/β-连环蛋白信号通路的激活通过激活 ZEB1 和 EMT 的其他激活剂增强脑胶质瘤细胞的体外迁移能力。

Activation of canonical WNT/β-catenin signaling enhances in vitro motility of glioblastoma cells by activation of ZEB1 and other activators of epithelial-to-mesenchymal transition.

机构信息

Division of Stereotactic Neurosurgery, Department of General Neurosurgery, University Medical Center Freiburg, Freiburg, Germany.

出版信息

Cancer Lett. 2012 Dec 1;325(1):42-53. doi: 10.1016/j.canlet.2012.05.024. Epub 2012 May 28.

Abstract

Here we show that activation of the canonical WNT/β-catenin pathway increases the expression of stem cell genes and promotes the migratory and invasive capacity of glioblastoma. Modulation of WNT signaling alters the expression of epithelial-to-mesenchymal transition activators, suggesting a role of this process in the regulation of glioma motility. Using immunohistochemistry in patient-derived glioblastoma samples we showed higher numbers of cells with intranuclear signal for β-catenin in the infiltrating edge of tumor compared to central tumor parenchyma. These findings suggest that canonical WNT/β-catenin pathway is a critical regulator of GBM invasion and may represent a potential therapeutic target.

摘要

在这里,我们表明经典 WNT/β-连环蛋白途径的激活会增加干细胞基因的表达,并促进神经胶质瘤的迁移和侵袭能力。WNT 信号的调节会改变上皮-间充质转化激活剂的表达,这表明该过程在调节神经胶质瘤的运动中起作用。通过对患者来源的神经胶质瘤样本进行免疫组织化学分析,我们发现与肿瘤中心实质相比,肿瘤浸润边缘的细胞中β-连环蛋白的核内信号数量更高。这些发现表明经典 WNT/β-连环蛋白途径是 GBM 侵袭的关键调节剂,可能代表一个潜在的治疗靶点。

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