FOXM1 通过刺激 Slug 在人乳腺癌中的转录促进上皮间质转化。

FOXM1 promotes the epithelial to mesenchymal transition by stimulating the transcription of Slug in human breast cancer.

机构信息

State Key Laboratory of Chemo/Biosensing and Chemometrics, College of Biology, Collaborative Innovation Center for Chemistry and Molecular Medicine, Hunan University, Changsha, Hunan 410082, China.

出版信息

Cancer Lett. 2013 Oct 28;340(1):104-12. doi: 10.1016/j.canlet.2013.07.004. Epub 2013 Jul 12.

DOI:10.1016/j.canlet.2013.07.004

PMID:23856032

Abstract

The Forkhead Box M1 (FOXM1) transcription factor is involved in tumorigenesis and tumor progression in multiple human carcinomas. In this study, we found that FOXM1 promoted the epithelial to mesenchymal transition (EMT) in human breast cancer. We observed a strong correlation between the expression levels of FOXM1 and the mesenchymal phenotype. Knockdown of FOXM1 inhibited the mesenchymal phenotype, whereas stable overexpression of FOXM1 induced EMT in breast cancer cells. FOXM1 was found to endogenously bind to and stimulate the promoter of Slug that is crucial for EMT progression. The knockdown of Slug abolished the EMT-inducing function of FOXM1. The stable overexpression of FOXM1 promoted metastasis of breast cancer cells in vivo. This study confirmed that FOXM1 promoted EMT in breast cancer cells by stimulating the transcription of EMT-related genes such as Slug.

摘要

叉头框蛋白 M1（FOXM1）转录因子参与多种人类癌中的肿瘤发生和肿瘤进展。在这项研究中，我们发现 FOXM1 促进了人类乳腺癌中的上皮间质转化（EMT）。我们观察到 FOXM1 的表达水平与间质表型之间存在很强的相关性。FOXM1 的敲低抑制了间质表型，而 FOXM1 的稳定过表达则诱导乳腺癌细胞发生 EMT。FOXM1 被发现内源性结合并刺激 EMT 进展至关重要的 Slug 启动子。Slug 的敲低消除了 FOXM1 的 EMT 诱导功能。FOXM1 的稳定过表达促进了乳腺癌细胞在体内的转移。这项研究证实，FOXM1 通过刺激 EMT 相关基因如 Slug 的转录来促进乳腺癌细胞的 EMT。