HMSN-Lom and Ndrg-1

[Guest guest]

(Note: I am posting this because there is mention of HMSN-Lom)

Carcinogenesis. 2006 Aug 18

The metastasis suppressor, Ndrg-1: a new ally in the fight against

cancer.

Kovacevic Z, DR.

Iron Metabolism and Chelation Program, Department of Pathology,

University of Sydney, Sydney, New South Wales, 2006 Australia.

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.