Department of Cellular and Molecular Pathology, German Cancer Research Centre (DKFZ), Heidelberg, Germany.
J Cell Physiol. 2011 Mar;226(3):710-9. doi: 10.1002/jcp.22385.
The Forkhead family of transcription factors comprises numerous members and is implicated in various cellular functions, including cell growth, apoptosis, migration, and differentiation. In this study, we identified the Forkhead factor FoxQ1 as increased in expression during TGF-β1 induced changes in epithelial differentiation, suggesting functional roles of FoxQ1 for epithelial plasticity. The repression of FoxQ1 in mammary epithelial cells led to a change in cell morphology characterized by an increase in cell size, pronounced cell-cell contacts, and an increased expression of several junction proteins (e.g., E-cadherin). In addition, FoxQ1 knock-down cells revealed rearrangements in the actin-cytoskeleton and slowed down cell cycle G1-phase progression. Furthermore, repression of FoxQ1 enhanced the migratory capacity of coherent mammary epithelial cells. Gene expression profiling of NM18 cells indicated that FoxQ1 is a relevant downstream mediator of TGF-β1-induced gene expression changes. This included the differential expression of transcription factors involved in epithelial plasticity, for example, Ets-1, Zeb1, and Zeb2. In summary, this study has elucidated the functional impact of FoxQ1 on epithelial differentiation.
叉头框转录因子家族包含众多成员，涉及多种细胞功能，包括细胞生长、凋亡、迁移和分化。在这项研究中，我们发现叉头因子 FoxQ1 在 TGF-β1 诱导的上皮分化变化中表达增加，表明 FoxQ1 对上皮可塑性具有功能作用。在乳腺上皮细胞中抑制 FoxQ1 会导致细胞形态发生变化，特征为细胞大小增加、细胞间接触明显、几种连接蛋白（如 E-钙粘蛋白）的表达增加。此外，FoxQ1 敲低细胞显示肌动蛋白细胞骨架的重排和细胞周期 G1 期进展减慢。此外，抑制 FoxQ1 增强了同源乳腺上皮细胞的迁移能力。NM18 细胞的基因表达谱分析表明，FoxQ1 是 TGF-β1 诱导的基因表达变化的一个相关下游介质。这包括参与上皮可塑性的转录因子的差异表达，例如 Ets-1、Zeb1 和 Zeb2。总之，本研究阐明了 FoxQ1 对上皮分化的功能影响。
