Overexpressed P75CUX1 promotes EMT in glioma infiltration by activating β-catenin.
Overexpressed P75CUX1 promotes EMT in glioma infiltration by activating β-catenin.
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过表达的 P75CUX1 通过激活 β-catenin 促进神经胶质瘤浸润中的 EMT
DOI：
10.1038/s41419-021-03424-1
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发表时间：
2021-02-04
影响因子：
9
通讯作者：
Song Y
中科院分区：
文献类型：
--
作者：
Xu A;Wang X;Luo J;Zhou M;Yi R;Huang T;Lin J;Wu Z;Xie C;Ding S;Zeng Y;Song Y
同源框蛋白切割样1（CUX 1）包括三种亚型，并已被证明参与各种类型的恶性肿瘤的发展。然而，CUX 1亚型在胶质瘤中的表达和作用仍不清楚。在此，我们首先鉴定了P75 CUX 1同种型在胶质瘤中的三种同种型中表现出一致的表达，并使用专门设计的抗体来鉴定所有CUX 1同种型。Western blot和免疫组化结果显示，P75 CUX 1在胶质瘤组织中的表达明显高于非肿瘤脑组织（NB），且P75 CUX 1的表达水平与肿瘤分级呈正相关。Kaplan-Meier生存分析提示P75 CUX 1可作为胶质瘤预后不良的独立指标。此外，CUX 1敲低抑制胶质瘤细胞在体外和体内的迁移和侵袭。本研究发现P75 CUX 1通过β-catenin介导的EMT过程，CUX 1/β-catenin/EMT是一个新的信号级联反应，介导胶质瘤的浸润。此外，CUX 1还通过Hippo、PI 3 K/AKT等多种信号通路促进胶质瘤的发生发展。结论：P75 CUX 1可能作为恶性胶质瘤的一个潜在的预后指标和新的治疗靶点。
The homeobox protein cut-like 1 (CUX1) comprises three isoforms and has been shown to be involved in the development of various types of malignancies. However, the expression and role of the CUX1 isoforms in glioma remain unclear. Herein, we first identified that P75CUX1 isoform exhibited consistent expression among three isoforms in glioma with specifically designed antibodies to identify all CUX1 isoforms. Moreover, a significantly higher expression of P75CUX1 was found in glioma compared with non-tumor brain (NB) tissues, analyzed with western blot and immunohistochemistry, and the expression level of P75CUX1 was positively associated with tumor grade. In addition, Kaplan–Meier survival analysis indicated that P75CUX1 could serve as an independent prognostic indicator to identify glioma patients with poor overall survival. Furthermore, CUX1 knockdown suppressed migration and invasion of glioma cells both in vitro and in vivo. Mechanistically, this study found that P75CUX1 regulated epithelial–mesenchymal transition (EMT) process mediated via β-catenin, and CUX1/β-catenin/EMT is a novel signaling cascade mediating the infiltration of glioma. Besides, CUX1 was verified to promote the progression of glioma via multiple other signaling pathways, such as Hippo and PI3K/AKT. In conclusion, we suggested that P75CUX1 could serve as a potential prognostic indicator as well as a novel treatment target in malignant glioma.
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