Carcinogenesis Advance Access published online on August 18, 2006
Carcinogenesis, doi:10.1093/carcin/bgl146
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1 Iron Metabolism and Chelation Program, Department of Pathology, University of Sydney, Sydney, New South Wales, 2006 Australia
* To whom correspondence should be addressed. Tumor metastasis is an important clinical problem, contributing to the majority of cancer-related deaths. The recent discovery of metastasis suppressor genes, such as N-myc downstream-regulated gene-1 (Ndrg-1), has introduced a novel approach to treating cancer and preventing metastasis. Ndrg-1 has been identified as a protein involved in the differentiation of epithelial cells. In addition, Ndrg-1 expression can be regulated by androgens and is involved in the pathology of the disease, Hereditary Motor and Sensory Neuropathy-Lom (HMSNL). However, one of the most well documented links between Ndrg-1 and pathophysiology is its association with inhibition of tumor metastasis. The expression of Ndrg-1 was found to be significantly down-regulated in a variety of different neoplasms including breast, colon and prostate cancer. Furthermore, Ndrg-1 expression was shown to be negatively correlated with tumor metastasis. Studies in vitro and in vivo have demonstrated a significant reduction in the metastatic ability of cells over-expressing Ndrg-1. The ability of these cells to invade was also compromised. The Gleason grade of prostate and breast cancers was found to correlate with Ndrg-1 expression, with more advanced and poorly differentiated tumors having lower Ndrg-1 levels. Recently, Ndrg-1 expression was demonstrated to be regulated by cellular iron levels and induced by iron chelators. These latter compounds were recently identified as potential anti-cancer agents as they selectively prevent cancer cell proliferation and lead to apoptosis. The discovery that iron chelators also increase Ndrg-1 expression further augments their anti-tumor activity and provides a novel strategy for the treatment of cancer and its metastasis.
Received June 3, 2006
Revised July 15, 2006
Accepted August 1, 2006
CANCER BIOLOGY
The metastasis suppressor, Ndrg-1: a new ally in the fight against cancer
Zaklina Kovacevic 1 and Des R. Richardson 1 *
Des R. Richardson, E-mail: d.richardson{at}med.usyd.edu.au
Abstract 
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