Department of Gynecology, Obstetrics & Gynecology Hospital, Fudan University, Shanghai, 200011, China.
Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Fudan University, Shanghai, 200032, China.
Cancer Lett. 2019 Mar 31;445:45-56. doi: 10.1016/j.canlet.2019.01.003. Epub 2019 Jan 14.
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.
转录因子 BTB 和 CNC 同源域 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的机制在很大程度上尚未确定。在这里，我们报告 Bach1 的表达在人上皮性卵巢癌（EOC）组织中明显高于正常卵巢组织，并且 Bach1 水平较高与肿瘤分期和总体生存率和无进展生存率较差相关。我们发现 Bach1 通过在人 EOC 细胞系 A2780 中募集 HMGA2 来增强上皮-间充质转化（EMT）基因的表达，包括 Slug 和 Snail，并促进细胞迁移。Bach1 的过表达增强了 Slug 的表达，并减少了 EOC 细胞在肿瘤转移小鼠模型中的转移，而 Bach1 的敲除则降低了 Slug 的表达和 EOC 细胞的转移。Bach1 的表达与人卵巢癌组织中 Slug 和 HMGA2 的表达呈正相关。此外，Bach1 激活了 p-AKT 和 p-p70S6K，增加了 cyclin D1 的表达，并促进了卵巢癌细胞在体外和体内肿瘤异种移植中的生长。总之，我们的研究结果表明 Bach1 增强了肿瘤的生长，并募集 HMGA2 来促进 EMT 和卵巢癌转移。
