Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2014 Nov 1;354(1):33-42.
doi: 10.1016/j.canlet.2014.06.023. Epub 2014 Aug 19.

N-myc downstream-regulated gene 2 (NDRG2) suppresses the epithelial-mesenchymal transition (EMT) in breast cancer cells via STAT3/Snail signaling

Myung-Jin Kim  1 , Jihyun Lim  1 , Young Yang  1 , Myeong-Sok Lee  1 , Jong-Seok Lim  2
Affiliations

N-myc downstream-regulated gene 2 (NDRG2) suppresses the epithelial-mesenchymal transition (EMT) in breast cancer cells via STAT3/Snail signaling

Myung-Jin Kim et al. Cancer Lett. .

Abstract

Although NDRG2 has recently been found to be a candidate tumor suppressor, its precise role in the epithelial-mesenchymal transition (EMT) is not well understood. In the present study, we demonstrated that NDRG2 overexpression in MDA-MB-231 cells down-regulated the expression of Snail, a transcriptional repressor of E-cadherin and a key regulator of EMT, as well as the phosphorylation of signal transducer and activator of transcription 3 (STAT3), an oncogenic transcription factor that is activated in many human malignancies including breast cancer. In addition, we confirmed that the expression of Snail and phospho-STAT3 was recovered when NDRG2 was knocked down by siRNA in MCF7 cells in which NDRG2 is endogenously expressed. Interestingly, MDA-MB-231-NDRG2 cells showed remarkably decreased Snail expression after treatment with JSI-124 (also known as cucurbitacin I) or Stattic, STAT3 inhibitors, compared to MDA-MB-231-mock cells. Moreover, STAT3 activation by EGF treatment induced higher Snail expression, and NDRG2 overexpression resulted in the inhibition of Snail expression in MDA-MB-231 cells stimulated by EGF in the absence or presence of STAT3 inhibitor. Treatment of MDA-MB-231 cells with STAT3 inhibitor led to a moderate decrease in wound healing and migration capacity, whereas STAT3 inhibitor treatment of MDA-MB-231-NDRG2 cells resulted in a significant attenuation of migration in both resting and EGF-stimulated cells. Collectively, our data demonstrate that the inhibition of STAT3 signaling by NDRG2 suppresses EMT progression of EMT via the down-regulation of Snail expression.

Keywords: Breast cancer; EMT; NDRG2; STAT3; Snail.

PubMed Disclaimer

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

Publication types

LinkOut - more resources

-