Carcinogenesis Advance Access originally published online on August 18, 2006
Carcinogenesis 2006 27(12):2355-2366; doi:10.1093/carcin/bgl146
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
The metastasis suppressor, Ndrg-1: a new ally in the fight against cancer
Iron Metabolism and Chelation Program, Department of Pathology, University of Sydney Sydney, New South Wales 2006, Australia
*To whom correspondence should be addressed. Tel: +61 2 9036 6548; Fax: +61 2 9036 6549 Email: d.richardson{at}med.usyd.edu.au
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 downregulated 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 overexpressing 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 anticancer 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 antitumor activity and provides a novel strategy for the treatment of cancer and its metastasis.
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  S. H. Schilling, A. B. Hjelmeland, D. R. Radiloff, I. M. Liu, T. P. Wakeman, J. R. Fielhauer, E. H. Foster, J. D. Lathia, J. N. Rich, X.-F. Wang, et al. NDRG4 Is Required for Cell Cycle Progression and Survival in Glioblastoma Cells J. Biol. Chem., September 11, 2009; 284(37): 25160 - 25169. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 F. Hosoi, H. Izumi, A. Kawahara, Y. Murakami, H. Kinoshita, M. Kage, K. Nishio, K. Kohno, M. Kuwano, and M. Ono N-myc Downstream Regulated Gene 1/Cap43 Suppresses Tumor Growth and Angiogenesis of Pancreatic Cancer through Attenuation of Inhibitor of {kappa}B Kinase {beta} Expression Cancer Res., June 15, 2009; 69(12): 4983 - 4991. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. Leth-Larsen, R. Lund, H. V. Hansen, A.-V. Laenkholm, D. Tarin, O. N. Jensen, and H. J. Ditzel Metastasis-related Plasma Membrane Proteins of Human Breast Cancer Cells Identified by Comparative Quantitative Mass Spectrometry Mol. Cell. Proteomics, June 1, 2009; 8(6): 1436 - 1449. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G. Bonuccelli, M. C. Casimiro, F. Sotgia, C. Wang, M. Liu, S. Katiyar, J. Zhou, E. Dew, F. Capozza, K. M. Daumer, et al. Caveolin-1 (P132L), a Common Breast Cancer Mutation, Confers Mammary Cell Invasiveness and Defines a Novel Stem Cell/Metastasis-Associated Gene Signature Am. J. Pathol., May 1, 2009; 174(5): 1650 - 1662. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Y.-J. Kim, S. Y. Yoon, J.-T. Kim, E. Y. Song, H. G. Lee, H. J. Son, S. Y. Kim, D. Cho, I. Choi, J. H. Kim, et al. NDRG2 expression decreases with tumor stages and regulates TCF/{beta}-catenin signaling in human colon carcinoma Carcinogenesis, April 1, 2009; 30(4): 598 - 605. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. J. Assinder, Q. Dong, H. Mangs, and D. R. Richardson Pharmacological Targeting of the Integrated Protein Kinase B, Phosphatase and Tensin Homolog Deleted on Chromosome 10, and Transforming Growth Factor-{beta} Pathways in Prostate Cancer Mol. Pharmacol., March 1, 2009; 75(3): 429 - 436. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. A. Meester-Smoor, M. J.F.W. Janssen, G. C. Grosveld, A. de Klein, W. F.J. van IJcken, H. Douben, and E. C. Zwarthoff MN1 affects expression of genes involved in hematopoiesis and can enhance as well as inhibit RAR/RXR-induced gene expression Carcinogenesis, October 1, 2008; 29(10): 2025 - 2034. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
X. Xu, R. Sutak, and D. R. Richardson Iron Chelation by Clinically Relevant Anthracyclines: Alteration in Expression of Iron-Regulated Genes and Atypical Changes in Intracellular Iron Distribution and Trafficking Mol. Pharmacol., March 1, 2008; 73(3): 833 - 844. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. Okuda, K. Kokame, and T. Miyata Differential Expression Patterns of NDRG Family Proteins in the Central Nervous System J. Histochem. Cytochem., February 1, 2008; 56(2): 175 - 182. [Abstract] [Full Text] [PDF]
|
|