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J Biol Chem. 2013 Apr 26;288(17):12222-31. doi: 10.1074/jbc.M112.434225. Epub 2013 Feb 28.

The transcription factor sterile alpha motif (SAM) pointed domain-containing ETS transcription factor (SPDEF) is required for E-cadherin expression in prostate cancer cells.

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1
Program in Urosciences, Division of Urology, Department of Surgery, School of Medicine, Aurora, Colorado 80045, USA.

Abstract

Loss of E-cadherin is one of the key steps in tumor progression. Our previous studies demonstrate that SAM pointed domain-containing ETS transcription factor (SPDEF) inhibited prostate cancer metastasis in vitro and in vivo. In the present study, we evaluated the relationship between SPDEF and E-cadherin expression in an effort to better understand the mechanism of action of SPDEF in prostate tumor cell invasion and metastasis. The results presented here demonstrate a direct correlation between expression of E-cadherin and SPDEF in prostate cancer cells. Additional data demonstrate that modulation of E-cadherin and SPDEF had similar effects on cell migration/invasion. In addition, siRNA-mediated knockdown of E-cadherin was sufficient to block the effects of SPDEF on cell migration and invasion. We also show that stable forced expression of SPDEF results in increased expression of E-cadherin, whereas down-regulation of SPDEF decreased E-cadherin expression. In addition, we demonstrate that SPDEF expression is not regulated by E-cadherin. Moreover, our chromatin immunoprecipitation and luciferase reporter assay revealed that SPDEF occupies E-cadherin promoter site and acts as a direct transcriptional inducer of E-cadherin in prostate cancer cells. Taken together, to the best of our knowledge, these studies are the first demonstrating requirement of SPDEF for expression of E-cadherin, an essential epithelial cell junction protein. Given that loss of E-cadherin is a central tenant in tumor metastasis, the results of our studies, by providing a new mechanism for regulation of E-cadherin expression, could have far reaching impact.

PMID:
23449978
PMCID:
PMC3636906
DOI:
10.1074/jbc.M112.434225
[Indexed for MEDLINE]
Free PMC Article
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