A systematic approach identifies FOXA1 as a key factor in the loss of epithelial traits during the epithelial-to-mesenchymal transition in lung cancer.
A systematic approach identifies FOXA1 as a key factor in the loss of epithelial traits during the epithelial-to-mesenchymal transition in lung cancer.
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系统方法确定 FOXA1 是肺癌上皮-间质转化过程中上皮特征丧失的关键因素
DOI：
10.1186/1471-2164-14-680
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发表时间：
2013-10-04
期刊：
影响因子：
4.4
通讯作者：
Liu XS
中科院分区：
文献类型：
--
作者：
Wang H;Meyer CA;Fei T;Wang G;Zhang F;Liu XS
肿瘤上皮细胞向间质细胞的转化是肿瘤转移的重要机制。虽然包括SNAIL、SLUG和TWIST1在内的转录因子调节了上皮细胞向间质细胞的转化，但其他未知的转录因子也可能参与其中。鉴定完整的转录因子对于更全面地了解这一过程中的基因调控至关重要。染色质免疫沉淀测序（ChIP-Seq）技术已被用于检测转录因子的全基因组结合；在这里，我们开发了一种系统的方法来整合现有的ChIP-Seq和转录组数据。我们扫描了多种转录因子，以研究它们在人A549肺腺癌细胞系上皮细胞向间质细胞转化过程中的功能影响。结果在检测的转录因子中，影响评分发现叉头盒蛋白A1 （FOXA1）是上皮细胞向间质细胞转化过程中最重要的转录因子。FOXA1在物理上与其预测的靶基因的启动子相关联。在FOXA1的调控网络中发现了几个参与细胞粘附和细胞通讯的关键上皮-间质转化效应因子，包括FOXA2、FGA、FGB、FGG和FGL1。FOXA1通过其调控网络参与上皮细胞向间质细胞的转化，提示FOXA1可能在肺癌转移的起始过程中发挥重要作用。结论FOXA1在肺癌转移初期可能是一个重要的转录因子和负调控因子。FOXA1可能通过其转录调控网络调控上皮细胞向间质细胞的转化。此外，本研究还展示了如何将ChIP-Seq和表达数据整合起来，以描述转录因子对特定生物过程的影响。
BackgroundThe epithelial-to-mesenchymal transition is an important mechanism in cancer metastasis. Although transcription factors including SNAIL, SLUG, and TWIST1 regulate the epithelial-to-mesenchymal transition, other unknown transcription factors could also be involved. Identification of the full complement of transcription factors is essential for a more complete understanding of gene regulation in this process. Chromatin immunoprecipitation-sequencing (ChIP-Seq) technologies have been used to detect genome-wide binding of transcription factors; here, we developed a systematic approach to integrate existing ChIP-Seq and transcriptome data. We scanned multiple transcription factors to investigate their functional impact on the epithelial-to-mesenchymal transition in the human A549 lung adenocarcinoma cell line.ResultsAmong the transcription factors tested, impact scores identified the forkhead box protein A1 (FOXA1) as the most significant transcription factor in the epithelial-to-mesenchymal transition. FOXA1 physically associates with the promoters of its predicted target genes. Several critical epithelial-to-mesenchymal transition effectors involved in cellular adhesion and cellular communication were identified in the regulatory network of FOXA1, including FOXA2, FGA, FGB, FGG, and FGL1. The implication of FOXA1 in the epithelial-to-mesenchymal transition via its regulatory network indicates that FOXA1 may play an important role in the initiation of lung cancer metastasis.ConclusionsWe identified FOXA1 as a potentially important transcription factor and negative regulator in the initial stages of lung cancer metastasis. FOXA1 may modulate the epithelial-to-mesenchymal transition via its transcriptional regulatory network. Further, this study demonstrates how ChIP-Seq and expression data could be integrated to delineate the impact of transcription factors on a specific biological process.
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影响因子：
5.3
作者：
Carver, EA;Jiang, RL;Gridley, T
通讯作者：
Gridley, T
影响因子：
11.2
作者：
Spaderna, Simone;Schmalhofer, Otto;Brabletz, Thomas
通讯作者：
Brabletz, Thomas
DOI：
10.1111/j.2517-6161.1995.tb02031.x
发表时间：
1995-01-01
影响因子：
5.8
作者：
BENJAMINI, Y;HOCHBERG, Y
通讯作者：
HOCHBERG, Y
影响因子：
14.9
作者：
Maglott D;Ostell J;Pruitt KD;Tatusova T
通讯作者：
Tatusova T
影响因子：
4.8
作者：
Rhodes, DR;Yu, JJ;Chinnaiyan, AM
通讯作者：
Chinnaiyan, AM