Snail is a repressor of RK1P transcription in metastatic prostate cancer cells
Snail is a repressor of RK1P transcription in metastatic prostate cancer cells
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DOI：
10.1038/sj.onc.1210860
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发表时间：
2008-04-03
期刊：
影响因子：
8
通讯作者：
Yeung, K. C.
中科院分区：
文献类型：
--
作者：
Beach, S.;Tang, H.;Yeung, K. C.
转移抑制蛋白RKIP的表达减少先前在许多癌症中被报道。潜在的机制仍然未知。在这里，我们发现RKIP的表达与Snail锌转录抑制因子的表达呈负相关，Snail锌转录抑制因子是正常和肿瘤性上皮间质转化（EMT）程序的关键调节因子。通过功能丧失和功能获得方法的结合，我们表明Snail抑制了转移性前列腺癌细胞系中RKIP的表达。Snail对RKIP的影响是在转录起始水平上，并通过RKIP启动子近端的E-box介导。因此，我们的研究结果表明，RKIP是一个新的组成部分的蜗牛转录调控网络的重要进展和转移的癌症。
Diminished expression of the metastasis suppressor protein RKIP was previously reported in a number of cancers. The underlying mechanism remains unknown. Here, we show that the expression of RKIP negatively correlates with that of Snail zinc-transcriptional repressor, a key modulator of normal and neoplastic epithelial-mesenchymal transition (EMT) program. With a combination of loss-of-function and gain-of-function approaches, we showed that Snail repressed the expression of RKIP in metastatic prostate cancer cell lines. The effect of Snail on RKIP was on the level of transcriptional initiation and mediated by a proximal E-box on the RKIP promoter. Our results therefore suggest that RKIP is a novel component of the Snail transcriptional regulatory network important for the progression and metastasis of cancer.