Tumor suppressor NDRG2 tips the balance of oncogenic TGF-b via EMT inhibition in colorectal cancer

72Citations
Citations of this article
34Readers
Mendeley users who have this article in their library.

This article is free to access.

Abstract

Transforming growth factor-beta (TGF-β), a pluripotent cytokine expressed in the colon, has a crucial but paradoxical role in colorectal cancer (CRC). TGF-β is a potent proliferation inhibitor of normal colon epithelial cells and acts as a tumor suppressor. However, TGF-β also promotes invasion and metastasis during late-stage CRC, thereby acting as an oncogene. Thus, understanding the factors behind the paradoxical roles of TGF-β and elucidating the mechanisms by which TGF-β-induced proliferation inhibition is impaired in CRC are necessary. Here, we found that the N-Myc tumor suppressor gene downstream-regulated gene NDRG2 (N-Myc downstream-regulated gene 2), which is a TGF-β-responsive gene, abrogated TGF-β-induced epithelial-mesenchymal transition (EMT) and further inhibited the invasion and migration of CRC cells. TGF-β positively induced NDRG2 expression through direct transactivation mediated by Sp1 and by abrogation of the repressive c-Myc/Miz-1 complex on NDRG2 promoter in normal epithelial cells. Aberrant hypermethylation of NDRG2, which could respond to TGF-β growth inhibition signaling, abrogated the inhibitory effect of NDRG2 in TGF-β-induced EMT in CRCs. Reduced NDRG2 expression was highly correlated with the invasion stage and metastasis of CRC. Our study establishes that NDRG2 is a new tumor suppressor gene that responds to TGF-β anti-proliferative signaling and tips the balance of oncogenic TGF-β during late-stage CRC.

Cite

CITATION STYLE

APA

Shen, L., Qu, X., Ma, Y., Zheng, J., Chu, D., Liu, B., … Zhang, J. (2014). Tumor suppressor NDRG2 tips the balance of oncogenic TGF-b via EMT inhibition in colorectal cancer. Oncogenesis, 3(2). https://doi.org/10.1038/oncsis.2013.48

Register to see more suggestions

Mendeley helps you to discover research relevant for your work.

Already have an account?

Save time finding and organizing research with Mendeley

Sign up for free