ZFP57 suppress proliferation of breast cancer cells through down-regulation of MEST-mediated Wnt/β-catenin signalling pathway
ZFP57 suppress proliferation of breast cancer cells through down-regulation of MEST-mediated Wnt/β-catenin signalling pathway
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ZFP57 通过下调 MEST 介导的 Wnt/β-catenin 信号通路抑制乳腺癌细胞增殖
DOI：
10.1038/s41419-019-1335-5
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发表时间：
2019-02-20
影响因子：
9
通讯作者：
Zheng, Mingjie
中科院分区：
文献类型：
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作者：
Chen, Lie;Wu, Xiaowei;Zheng, Mingjie
通过启动子低甲基化激活癌基因在肿瘤发生中起着重要作用。锌指蛋白57 （ZFP57）是kraf - zfps的一个成员，可以维持胚胎干细胞（ESCs）的DNA甲基化，尽管其在乳腺癌中的作用和潜在机制尚不清楚。在本研究中，我们发现ZFP57在乳腺癌中低表达，过表达ZFP57可以通过抑制Wnt/ β -catenin通路抑制乳腺癌细胞的增殖。MEST被证实为ZFP57的直接靶基因，ZFP57可能通过保持DNA甲基化而下调MEST。此外，MEST的过表达可以恢复ZFP57的肿瘤抑制作用和Wnt/ β -catenin通路的失活作用。ZFP57-MEST和Wnt/ β -catenin通路轴参与乳腺肿瘤发生，这可能代表一种潜在的诊断生物标志物，并为乳腺癌患者提供新的治疗策略提供新的见解。
Activation of oncogenes by promoter hypomethylation plays an important role in tumorigenesis. Zinc finger protein 57 (ZFP57), a member of KRAB-ZFPs, could maintain DNA methylation in embryonic stem cells (ESCs), although its role and underlying mechanisms in breast cancer are not well understood. In this study, we found that ZFP57 had low expression in breast cancer, and overexpression of ZFP57 could inhibit the proliferation of breast cancer cells by inhibiting the Wnt/beta-catenin pathway. MEST was validated as the direct target gene of ZFP57 and MEST may be down-regulated by ZFP57 through conserving DNA methylation. Furthermore, overexpression of MEST could restore the tumour-suppressed and the Wnt/beta-catenin pathway inactivated effects of ZFP57. ZFP57-MEST and the Wnt/beta-catenin pathway axis are involved in breast tumorigenesis, which may represent a potential diagnostic biomarker, and provide a new insight into a novel therapeutic strategy for breast cancer patients.