Sox4 stimulates β-catenin activity through induction of CK2
Sox4 stimulates β-catenin activity through induction of CK2
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DOI：
10.3892/or.2010.1091
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发表时间：
2011-02-01
期刊：
影响因子：
4.2
通讯作者：
Kim, Soo-A
中科院分区：
文献类型：
--
作者：
Lee, Ae-Kyung;Ahn, Sang-Gun;Kim, Soo-A
β-catenin 是 Wnt 信号通路的关键组成部分，β-catenin 的异常积累是各种癌症的特征。在这里，我们证明 Sox4 的过度表达通过增加 β-catenin 的稳定性来增强 β-catenin/TCF 活性。 Sox4 以剂量依赖性方式增加 β-catenin 及其靶基因 cyclin D1 的蛋白水平。 Sox4 的 siRNA 实验还表明，Sox4 会增加 β-catenin 的蛋白水平，从而激活 Wnt 信号通路。我们发现 Sox4 诱导 β-连环蛋白/TCF 活性是由 β-连环蛋白的稳定作用引起的，而不是由诱导 β-连环蛋白转录引起的。我们进一步证明 β-连环蛋白水平的增加是由 CK2 的诱导引起的。鉴于最近的证据表明 Sox4 表达在结肠和其他β-连环蛋白失调的肿瘤中被激活，我们的研究结果表明 Sox4 在癌细胞中充当 Wnt 信号传导的激动剂。
beta-catenin is a key component of the Wnt signaling pathway and the abnormal accumulation of beta-catenin is characteristic of various types of cancer. Here we demonstrate that overexpression of Sox4 enhances beta-catenin/TCF activity by increasing the stability of beta-catenin. Sox4 increased the protein level of beta-catenin and its target gene cyclin D1 in a dose-dependent manner. An siRNA experiment for Sox4 also demonstrated that Sox4 increases the protein levels of beta-catenin and thus activates the Wnt signaling pathway. We found that induction of beta-catenin/TCF activity by Sox4 is caused by stabilization of the beta-catenin protein, but not by induction of beta-catenin transcription. We further demonstrate that the increased level of beta-catenin is caused by induction of CK2. In light of recent evidence that Sox4 expression is activated in the colon and in other tumors with beta-catenin dysregulation, our findings suggest that Sox4 acts as an agonist of Wnt signaling in cancer cells.