Snail is a repressor of RKIP transcription in metastatic prostate cancer cells.
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.
Beach
S
S
Department of Biochemistry and Cancer Biology, College of Medicine, University of Toledo, Toledo, OH 43614-5804, USA.
Tang
H
H
Park
S
S
Dhillon
A S
AS
Keller
E T
ET
Kolch
W
W
Yeung
K C
KC
D030541:Databases, Genetic; D018450:Disease Progression; D015536:Down-Regulation; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008297:Male; D016555:Matched-Pair Analysis; D009362:Neoplasm Metastasis; D020411:Oligonucleotide Array Sequence Analysis; D049488:Phosphatidylethanolamine Binding Protein / Q000235:genetics*; D011401:Promoter Regions, Genetic; D011471:Prostatic Neoplasms / Q000235:genetics / Q000473:pathology*; D012097:Repressor Proteins / Q000502:physiology; D000071250:Snail Family Transcription Factors; D014157:Transcription Factors / Q000502:physiology*; D014158:Transcription, Genetic; D014162:Transfection; D014407:Tumor Cells, Cultured
C511482:PEBP1 protein, human; D049488:Phosphatidylethanolamine Binding Protein; D012097:Repressor Proteins; D000071250:Snail Family Transcription Factors; D014157:Transcription Factors