MUC1-C oncoprotein activates the ZEB1/miR-200c regulatory loop and epithelial-mesenchymal transition.
MUC1-C oncoprotein activates the ZEB1/miR-200c regulatory loop and epithelial-mesenchymal transition.
复制标题
作者：
上皮-间质转化（EMT）在癌细胞中被ZEB 1激活，ZEB 1是转录抑制因子的锌指/同源结构域家族的成员。粘蛋白1（MUC 1）异二聚体蛋白在人癌细胞中异常过表达。目前在乳腺癌细胞中的研究表明，致癌MUC 1-C亚基通过NF-κB（核因子κ B）p65依赖性机制诱导ZEB 1的表达。MUC 1-C与NF-κB p65一起占据ZEB 1启动子，从而促进ZEB 1转录。反过来，ZEB 1与MUC 1-C结合，ZEB 1/MUC 1-C复合物有助于miR-200 c的转录抑制，miR-200 c是上皮分化的诱导物。ZEB 1的协同上调和miR-200 c的抑制与上皮-间质转化（EMT）的诱导有关。与MUC 1-C对ZEB 1和miR-200 c的作用一致，我们表明MUC 1-C通过ZEB 1介导的机制诱导EMT和细胞侵袭。这些发现表明：（i）MUC 1-C激活ZEB 1并抑制miR-200 c，诱导EMT;（ii）靶向MUC 1-C可能是治疗乳腺癌和可能发展EMT特性的其他类型癌症的有效方法。
The epithelial–mesenchymal transition (EMT) is activated in cancer cells by ZEB1, a member of the zinc finger/homeodomain family of transcriptional repressors. The mucin 1 (MUC1) heterodimeric protein is aberrantly overexpressed in human carcinoma cells. The present studies in breast cancer cells demonstrate that the oncogenic MUC1-C subunit induces expression of ZEB1 by a NF-κB (nuclear factor kappa B) p65-dependent mechanism. MUC1-C occupies the ZEB1 promoter with NF-κB p65 and thereby promotes ZEB1 transcription. In turn, ZEB1 associates with MUC1-C and the ZEB1/MUC1-C complex contributes to the transcriptional suppression of miR-200c, an inducer of epithelial differentiation. The co-ordinate upregulation of ZEB1 and suppression of miR-200c has been linked to the induction of epithelial-mesenchymal transition (EMT). In concert with the effects of MUC1-C on ZEB1 and miR-200c, we show that MUC1-C induces EMT and cellular invasion by a ZEB1-mediated mechanism. These findings indicate that (i) MUC1-C activates ZEB1 and suppresses miR-200c with the induction of EMT and (ii) targeting MUC1-C could be an effective approach for the treatment of breast and possibly other types of cancers that develop EMT properties.
登录
查看更多内容
影响因子：
50.3
作者：
Ren, J;Agata, N;Kufe, D
通讯作者：
Kufe, D
影响因子：
11.2
作者：
Bracken, Cameron P.;Gregory, Philip A.;Goodall, Gregory J.
通讯作者：
Goodall, Gregory J.
影响因子：
5.2
作者：
Raina D;Ahmad R;Rajabi H;Panchamoorthy G;Kharbanda S;Kufe D
通讯作者：
Kufe D
影响因子：
4.8
作者：
Rajabi, Hasan;Ahmad, Rehan;Kufe, Donald
通讯作者：
Kufe, Donald
影响因子：
78.5
作者：
Kufe, Donald W.
通讯作者：
Kufe, Donald W.