BTB and CNC homology 1 (Bach1) promotes human ovarian cancer cell metastasis by HMGA2-mediated epithelial-mesenchymal transition

作者：Han, Wenyan; Zhang, Yiqun; Niu, Cong; Guo, Jieyu; Li, Jiajia; Wei, Xiangxiang; Jia, Mengping; Zhi, Xiuling^*; Yao, Liangqing^*; Meng, Dan^*

来源：Cancer Letters, 2019, 445: 45-56.

DOI：10.1016/j.canlet.2019.01.003

• Bach1
• Epithelial ovarian cancer metastasis
• Epithelial-mesenchymal transition (EMT)
• HMGA2
• Tumor growth

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.

• 出版日期2019
• 单位复旦大学