12-O-Tetradecanoylphorbol-13-acetate Promotes Breast Cancer Cell Motility by Increasing S100A14 Level in a Kruppel-like Transcription Factor 4 ( KLF4)-dependent Manner
12-O-Tetradecanoylphorbol-13-acetate Promotes Breast Cancer Cell Motility by Increasing S100A14 Level in a Kruppel-like Transcription Factor 4 ( KLF4)-dependent Manner
复制标题
12-O-十四烷酰佛波醇-13-乙酸酯通过以 Kruppel 样转录因子 4 (KLF4) 依赖性方式增加 S100A14 水平来促进乳腺癌细胞运动
DOI：
10.1074/jbc.m113.534271
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发表时间：
2014-03-28
影响因子：
4.8
通讯作者：
Liu, Zhihua
中科院分区：
文献类型：
--
作者：
He, Huan;Li, Sheng;Liu, Zhihua
背景：S100 A14的转录调控及其机制尚未完全阐明。结果：KLF 4激活S100 A14启动子后，TPA刺激S100 A14启动子表达上调。结论：S100 A14部分介导TPA诱导的细胞运动，其机制依赖于KLF 4。重要性：KLF 4在S100 A14的调节中起着重要的作用，但以前未被认识到。S100蛋白家族代表了钙结合EF-手型蛋白的最大亚群。据报道，这些蛋白质参与了与正常细胞发育和肿瘤发生相关的广泛的生物学功能。S100 A14是最近鉴定的S100蛋白家族的成员，并且在许多不同的人类恶性肿瘤中差异表达。然而，S100 A14的转录调控及其在乳腺癌中的作用需要进一步研究。在这里，我们确定，12-O-十四酰基佛波醇-13-乙酸酯（TPA）上调KLF 4的表达，并促进其直接结合到两个保守的GC丰富的DNA片段内的S100 A14启动子，这是必不可少的KLF 4诱导的S100 A14表达的反式激活。此外，KLF 4的稳定沉默显著抑制TPA诱导的乳腺癌细胞迁移。总的来说，这些结果提供了对TPA通过以KLF 4依赖性方式调节S100 A14的表达和功能来激发细胞运动性的事实的见解。
Background: The transcriptional regulation of S100A14 and its underlying mechanism have not been fully elucidated. Results: The activation of S100A14 promoter by KLF4 mediates its up-regulation upon TPA stimulation. Conclusion: S100A14 partly mediates TPA-induced cell motility in a KLF4-dependent manner. Significance: KLF4 plays a significant and previously unrecognized role in regulation of S100A14.The S100 protein family represents the largest subgroup of calcium binding EF-hand type proteins. These proteins have been reported to be involved in a wide range of biological functions that are related to normal cell development and tumorigenesis. S100A14 is a recently identified member of the S100 protein family and differentially expressed in a number of different human malignancies. However, the transcriptional regulation of S100A14 and its role in breast cancer needs to be further investigated. Here, we determined that 12-O-tetradecanoylphorbol-13-acetate (TPA) up-regulated the expression of KLF4 and facilitated its binding directly to two conserved GC-rich DNA segments within the S100A14 promoter, which is essential for the transactivation of KLF4 induced S100A14 expression. Furthermore, stable silencing of KLF4 significantly suppressed breast cancer cell migration induced by TPA. Collectively, these results offer insights into the fact that TPA provokes cell motility through regulating the expression and function of S100A14 in a KLF4-dependent manner.