Kindlin-2 interacts with β-catenin and YB-1 to enhance EGFR transcription during glioma progression.
Kindlin-2 interacts with β-catenin and YB-1 to enhance EGFR transcription during glioma progression.
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Kindlin-2 与 β-连环蛋白和 YB-1 相互作用，增强胶质瘤进展过程中的 EGFR 转录
DOI：
10.18632/oncotarget.12439
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发表时间：
2016-11-15
期刊：
影响因子：
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通讯作者：
Zhan Q
中科院分区：
文献类型：
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作者：
Ou Y;Zhao Z;Zhang W;Wu Q;Wu C;Liu X;Fu M;Ji N;Wang D;Qiu J;Zhang L;Yu C;Song Y;Zhan Q
Kindlin-2通过调节细胞-细胞和细胞-细胞外基质粘附促进癌发生。然而，Kindlin-2在胶质瘤中的作用尚未阐明。我们研究了188例人脑胶质瘤组织样本中Kindlin-2的表达。Kindlin-2的高表达与肿瘤的病理分级和预后有关。Kindlin-2促进胶质瘤细胞在体外和体内的运动和增殖。重要的是，Kindlin-2激活EGFR通路并增加EGFR mRNA水平。Kindlin-2除了上调Y-box结合蛋白-1（YB-1）和β-catenin表达外，还与YB-1和β-catenin形成转录复合物，结合EGFR启动子并增强转录。β-catenin/YB-1/EGFR通路是Kindlin-2介导的功能所必需的。我们的数据提供了一个更好的理解胶质瘤进展的机制，并建议Kindlin-2可能是胶质瘤的生物标志物和治疗靶点。
Kindlin-2 promotes carcinogenesis through regulation of cell-cell and cell-extracellular matrix adhesion. However, the role of Kindlin-2 in glioma has not been elucidated. We investigated Kindlin-2 expression in 188 human glioma tissue samples. High Kindlin-2 expression was correlated with high pathological grade and a worse prognosis. Kindlin-2 promoted glioma cell motility and proliferation both in vitro and in vivo. Importantly, Kindlin-2 activated the EGFR pathway and increased EGFR mRNA levels. In addition to up-regulating Y-box binding protein-1 (YB-1) and β-catenin expression, Kindlin-2 formed a transcriptional complex with YB-1 and β-catenin that bound to the EGFR promoter and enhanced transcription. The β-catenin/YB-1/EGFR pathway was required for Kindlin-2-mediated functions. Our data provide a better understanding of the mechanisms underlying glioma progression, and suggest that Kindlin-2 may be a biomarker and therapeutic target in glioma.