BTB and CNC homology 1 (Bach1) promotes human ovarian cancer cell metastasis by HMGA2-mediated epithelial-mesenchymal transition
BTB and CNC homology 1 (Bach1) promotes human ovarian cancer cell metastasis by HMGA2-mediated epithelial-mesenchymal transition
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BTB和CNC同源1（Bach1）通过HMGA2介导的上皮间质转化促进人卵巢癌细胞转移
DOI：
10.1016/j.canlet.2019.01.003
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发表时间：
2019-01-01
期刊：
影响因子：
9.7
通讯作者：
Meng, Dan
中科院分区：
文献类型：
--
作者：
Han, Wenyan;Zhang, Yiqun;Meng, Dan
转录因子BTB和CnC同源1(Bach1)与肿瘤的进展和转移有关，但Bach1对肿瘤生长和转移的影响机制尚不清楚。在此，我们报道了Bach1在上皮性卵巢癌(EOC)组织中的表达显著高于在正常卵巢组织中的表达，并且高水平的Bach1与肿瘤分期和较差的总体和无进展生存期有关。我们发现Bach1通过募集HMGA2促进人EoC细胞株A2780上皮-间充质转化(EMT)基因的表达，包括Slug和Snail，并促进细胞迁移。在肿瘤转移小鼠模型中，Bach1过表达增强和Bach1基因敲除降低了Slug的表达和EoC细胞的转移。卵巢癌组织中Bach1的表达与Slug和HMGA2的表达呈正相关。此外，Bach1还可激活p-AKT和p-p70S6K，上调细胞周期蛋白D1的表达，促进卵巢癌细胞的体外生长和体内移植瘤的生长。总之，我们的发现表明，Bach1促进了肿瘤的生长，并招募HMGA2来促进EMT和卵巢癌的转移。
Transcriptional factor BTB and CNC homology 1 (Bach1) has been linked to tumor progression and metastasis, but the mechanisms underlying the effects of Bach1 on tumor growth and metastasis are largely uncharacterized. Here, we report that Bach1 expression was significantly higher in human epithelial ovarian cancer (EOC) tissues than in normal ovarian tissues and that higher levels of Bach1 were associated with tumor stage and poorer overall and progression-free survival. We found that Bach1 enhanced the expression of epithelial-mesenchymal transition (EMT) genes, including Slug and Snail, and promoted cell migration by recruiting HMGA2 in the human EOC cell line A2780. Bach1 overexpression enhanced and Bach1 knockout reduced the expression of Slug and the metastasis of EOC cells in a tumor metastasis mouse model. Bach1 expression was positively correlated with Slug and HMGA2 expression in human ovarian cancer tissues. In addition, Bach1 activated p-AKT and p-p70S6K, increased the expression of cyclin D1, and promoted the growth of ovarian cancer cells in vitro and tumor xenografts in vivo. Together, our findings reveal that Bach1 enhances tumor growth and recruits HMGA2 to promote EMT and ovarian cancer metastasis.