Inserm U1052, Centre de Recherche en Cancérologie de Lyon, F-69000 Lyon, France; CNRS UMR5286, F-69000 Lyon, France; Centre Léon Bérard, F-69000 Lyon, France.
EMBO Rep. 2011 Jul 1;12(7):665-72. doi: 10.1038/embor.2011.78.
TGF-β is a potent inducer of epithelial-to-mesenchymal transition (EMT), a process involved in tumour invasion. TIF1γ participates in TGF-β signalling. To understand the role of TIF1γ in TGF-β signalling and its requirement for EMT, we analysed the TGF-β1 response of human mammary epithelial cell lines. A strong EMT increase was observed in TIF1γ-silenced cells after TGF-β1 treatment, whereas Smad4 inactivation completely blocked this process. Accordingly, the functions of several TIF1γ target genes can be linked to EMT, as shown by microarray analysis. As a negative regulator of Smad4, TIF1γ could be crucial for the regulation of TGF-β signalling. Furthermore, TIF1γ binds to and represses the plasminogen activator inhibitor 1 promoter, demonstrating a direct role of TIF1γ in TGF-β-dependent gene expression. This study shows the molecular relationship between TIF1γ and Smad4 in TGF-β signalling and EMT.
TGF-β 是上皮间质转化（EMT）的有效诱导剂，而 EMT 是肿瘤侵袭的一个过程。TIF1γ 参与 TGF-β 信号通路。为了理解 TIF1γ 在 TGF-β 信号通路中的作用及其 EMT 的必要性，我们分析了人乳腺上皮细胞系对 TGF-β1 的反应。TIF1γ 沉默的细胞在 TGF-β1 处理后 EMT 明显增加，而 Smad4 失活则完全阻断了这一过程。因此，通过微阵列分析，一些 TIF1γ 靶基因的功能可以与 EMT 相关联。TIF1γ 作为 Smad4 的负调节剂，对于 TGF-β 信号通路的调控可能至关重要。此外，TIF1γ 与纤溶酶原激活物抑制剂 1 启动子结合并抑制其表达，证明 TIF1γ 在 TGF-β 依赖性基因表达中具有直接作用。本研究显示了 TIF1γ 和 Smad4 在 TGF-β 信号通路和 EMT 中的分子关系。
