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

Abstract

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.

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Acknowledgements

We thank Stephen J Weiss and Mien-Chie Hung for plasmid constructs. We also acknowledge Chinnaiyan's lab and Robert Trumbly for help in studying the expression correlation of RKIP and Snail in prostate cancer. This work was supported by NIH grants to KCY (R01 GM64767) and ETK (R01 CA098513); and a UTHSC Translational Research Stimulation Award, to KCY. AD and WK are supported by the Cancer Research UK.

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Correspondence to K C Yeung.

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Beach, S., Tang, H., Park, S. et al. Snail is a repressor of RKIP transcription in metastatic prostate cancer cells. Oncogene 27, 2243–2248 (2008). https://doi.org/10.1038/sj.onc.1210860

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