Snail is a repressor of RK1P transcription in metastatic prostate cancer cells

被引:142
作者
Beach, S. [1 ]
Tang, H. [1 ]
Park, S. [1 ]
Dhillon, A. S. [4 ]
Keller, E. T. [2 ,3 ]
Kolch, W. [3 ,5 ]
Yeung, K. C. [1 ]
机构
[1] Univ Toledo, Coll Med, Dept Biochem & Canc Biol, Toledo, OH 43614 USA
[2] Univ Michigan Hlth Syst, Ctr Comprehens Canc, Ann Arbor, MI USA
[3] Univ Michigan Hlth Syst, Dept Urol, Ann Arbor, MI USA
[4] Beatson Inst Canc Res, Glasgow G61 1BD, Lanark, Scotland
[5] Univ Glasgow, Sir Henry Wellcome Funct Genom Facil, Glasgow G12 8QQ, Lanark, Scotland
关键词
regulation of RKIP expression; EMT; prostate cancer metastasis;
D O I
10.1038/sj.onc.1210860
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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.
引用
收藏
页码:2243 / 2248
页数:6
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