Department of Biochemistry, Dongguk University College of Oriental Medicine, Gyeongju 780-714, Republic of Korea.
Oncol Rep. 2011 Feb;25(2):559-65. doi: 10.3892/or.2010.1091. Epub 2010 Dec 9.
ß-catenin is a key component of the Wnt signaling pathway and the abnormal accumulation of ß-catenin is characteristic of various types of cancer. Here we demonstrate that overexpression of Sox4 enhances ß-catenin/TCF activity by increasing the stability of ß-catenin. Sox4 increased the protein level of ß-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 ß-catenin and thus activates the Wnt signaling pathway. We found that induction of ß-catenin/TCF activity by Sox4 is caused by stabilization of the ß-catenin protein, but not by induction of ß-catenin transcription. We further demonstrate that the increased level of ß-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 ß-catenin dysregulation, our findings suggest that Sox4 acts as an agonist of Wnt signaling in cancer cells.
ß-连环蛋白是 Wnt 信号通路的关键组成部分，ß-连环蛋白的异常积累是各种类型癌症的特征。在这里，我们证明 Sox4 通过增加 ß-连环蛋白的稳定性来增强 ß-连环蛋白/TCF 活性。Sox4 以剂量依赖性方式增加 ß-连环蛋白及其靶基因 cyclin D1 的蛋白水平。针对 Sox4 的 siRNA 实验也表明 Sox4 增加了 ß-连环蛋白的蛋白水平，从而激活了 Wnt 信号通路。我们发现 Sox4 通过诱导 ß-连环蛋白/TCF 活性引起 ß-连环蛋白蛋白的稳定，但不是通过诱导 ß-连环蛋白转录。我们进一步证明，β-连环蛋白水平的升高是由 CK2 的诱导引起的。鉴于 Sox4 表达在结肠和其他β-连环蛋白失调的肿瘤中被激活的最新证据，我们的研究结果表明 Sox4 在癌细胞中充当 Wnt 信号的激动剂。
