Sox5 induces epithelial to mesenchymal transition by transactivation of Twist1
Sox5 induces epithelial to mesenchymal transition by transactivation of Twist1
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Sox5 通过 Twist1 的反式激活诱导上皮细胞向间质细胞的转变
DOI：
10.1016/j.bbrc.2014.02.109
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发表时间：
2014-03-28
影响因子：
3.1
通讯作者：
Li, Hui-Xiang
中科院分区：
文献类型：
--
作者：
Pei, Xin-Hong;Lv, Xin-Quan;Li, Hui-Xiang
上皮间质转化（EMT）是一种高度保守的细胞程序，在正常胚胎发生和癌症转移中发挥着重要作用。 Twist1 是胚胎形态发生的主要调节因子，在乳腺癌中过度表达，并通过促进 EMT 促进转移。在探索乳腺癌细胞中Twist1增加的机制时，我们发现转录因子SRY（性别决定区Y）-box 5（Sox5）在乳腺癌细胞中上调，并且Sox5的耗竭会抑制乳腺癌细胞的增殖、迁移和侵袭。此外，乳腺癌细胞中 Sox5 的缺失导致 Twist1 急剧减少，染色体免疫沉淀测定表明 Sox5 可以直接与 Twist1 启动子结合，表明 Sox5 反式激活 Twist1 表达。我们进一步证明，敲除Sox5会上调上皮表型细胞生物标志物（E-钙粘蛋白）并下调间充质表型细胞生物标志物（N-钙粘蛋白、波形蛋白和纤连蛋白1），从而抑制EMT。我们的研究表明，Sox5 反式激活 Twist1 表达，并在调节乳腺癌进展中发挥重要作用。 (c) 2014 Elsevier Inc. 保留所有权利。
The epithelial to mesenchymal transition (EMT), a highly conserved cellular program, plays an important role in normal embryogenesis and cancer metastasis. Twist1, a master regulator of embryonic morphogenesis, is overexpressed in breast cancer and contributes to metastasis by promoting EMT. In exploring the mechanism underlying the increased Twist1 in breast cancer cells, we found that the transcription factor SRY (sex-determining region Y)-box 5(Sox5) is up-regulation in breast cancer cells and depletion of Sox5 inhibits breast cancer cell proliferation, migration, and invasion. Furthermore, depletion of Sox5 in breast cancer cells caused a dramatic decrease in Twist1 and chromosome immunoprecipitation assay showed that Sox5 can bind directly to the Twist1 promoter, suggesting that Sox5 transactivates Twist1 expression. We further demonstrated that knockdown of Sox5 up-regulated epithelial phenotype cell biomarker (E-cadherin) and down-regulated mesenchymal phenotype cell biomarkers (N-cadherin, Vimentin, and Fibronectin 1), resulting in suppression of EMT. Our study suggests that Sox5 transactivates Twist1 expression and plays an important role in the regulation of breast cancer progression. (c) 2014 Elsevier Inc. All rights reserved.