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Title 

NDRG2 positively regulates E-cadherin expression and prolongs overall survival in colon cancer patients

Authors 

Y J KimHo Bum KangH S YimJ H KimJae Wha Kim

Publisher 

Spandidos Publications

Issue Date 

2013

Citation 

Oncology Reports, vol. 30, no. 4, pp. 1890-1898

Keywords 

E-cadherinEpithelial-mesenchymal transitionGlycogen synthase kinase 3β phosphorylationN-Myc downstream-regulated gene 2Snail

Abstract 

To discover the molecular mechanism of N-Myc downstream-regulated gene 2 (NDRG2), a newly found differentiation-related tumor suppressor, the relationships between NDRG2 and E-cadherin were investigated in tumor cells and tissues. Positive correlations between the expression of E-cadherin and NDRG2 were shown in several colon cancer cell lines as well as in colon cancer tissues. According to the transcription assays using a reporter plasmid containing E-cadherin promoter region (-368~+51), NDRG2 introduction into colon cancer cell lines induced upregulation of E-cadherin promoter activity and its transcription. On the contrary, inhibition of NDRG2 expression by siRNA treatment caused the decrease of E-cadherin transcription. Snail, a zinc-finger transcriptional repressor, was shown to be a mediator of NDRG2-regulated E-cadherin expression. The enhancement of glycogen synthase kinase 3β (GSK-3β) activity by NDRG2 overexpression caused proteasomal degradation of Snail transcription factor followed by transcriptional de-repression of E-cadherin. We also found that NDRG2 could mediate cell density-regulated E-cadherin expression. The increase of NDRG2 expression with cell density preceded E-cadherin expression, and the regulation of Snail activity by GSK-3β was also related to this process.

ISSN 

1021-335X

Link 

http://dx.doi.org/10.3892/or.2013.2642

Appears in Collections

1. Journal Articles > Journal Articles

Registered Date

2019-05-02


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