The iron-regulated metastasis suppressor, Ndrg-1: Identification of novel molecular targets

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• 作者：Zaklina Kovacevic ; Dong Fu ; Des R. Richardson
• 关键词：Iron chelator ; Iron ; Desferioxamine ; Ndrg-1 ; Metastasis suppressor
• 刊名：Biochimica et Biophysica Acta (BBA)/Molecular Cell Research
• 出版年：2008
• 出版时间：October 2008
• 年：2008
• 卷：1783
• 期：10
• 页码：1981-1992
• 全文大小：1614 K

文摘

A recently identified metastasis suppressor, N-myc downstream regulated gene-1 (Ndrg-1), has been shown to reduce the invasion and metastasis of breast, colon, prostate and pancreatic cancer. Among its many functions, Ndrg-1 is involved in modulating differentiation, proliferation and angiogenesis. However, knowledge of the molecular targets of Ndrg-1 is limited. The current study has focused on examining the functions of Ndrg-1 in a number of different cancer cell models including prostate, colon, lung and pancreatic cancer to elucidate the known pleiotropic nature of this protein. Furthermore, the potential gene targets of Ndrg-1 were analyzed using whole genome gene array revealing a substantial number of genes whose expression was affected by this metastasis suppressor. Significantly, Ndrg-1 up-regulated thiamine triphosphatase (Thtpa) expression in three of the four cell models. Thtpa is known to decrease the levels of the energy currency molecule, thiamine triphosphate, suggesting a potential pathway for the anti-proliferative effects of Ndrg-1. Furthermore, Ndrg-1 reduced the protein levels of cathepsin C which plays a role in invasion, indicating a potential mechanism of its anti-metastatic role in pancreatic cancer cells. These findings provide a potential link between the observed functions of Ndrg-1 and its molecular targets, further demonstrating its anti-metastatic effect.