I'm a PhD candidate at The University of Sydney studying cancer cell biology
Metastasis, spreading of malignant cancer cells from the original site to distant organs, is a major cause of death in cancer patients. This highly complex process involves multiple steps, where the tumor cells transform in shape (epithelial to mesenchymal transition), migrate, invade, and form a new colony at their targeted site. These steps are driven by activation of oncogenes (molecules that contribute to cancer progression) and deactivation of tumour and/or metastasis suppressor (molecules that inhibit cancer progression).
The N-myc downstream-regulated gene 1 (NDRG1) is a well-known metastasis suppressor, which has been shown to inhibit metastasis in cancers of the prostate, pancreas, colon and breast. Intriguingly, however, this same molecule has been reported to promote metastasis in liver cancer. The exact mechanism(s) underlying these pleiotropic (opposing) behaviours of NDRG1 are yet unknown.
My research investigates this fascinating metastasis suppressor and its differential behaviours in different cancer-types. This research will reveal new and exciting aspects of NDRG1, which is important, as the molecule is a promising target for development of potent anti-metastatic therapeutics.
Abstract: N-myc down-regulated gene 1 (NDRG1) is a known metastasis suppressor in multiple cancers, being also involved in embryogenesis and development, cell growth and differentiation, lipid biosynthesis and myelination, stress responses and immunity. In addition to its primary role as a metastasis suppressor, NDRG1 can also influence other stages of carcinogenesis, namely angiogenesis and primary tumour growth. NDRG1 is regulated by multiple effectors in normal and neoplastic cells, including N-myc, histone acetylation, hypoxia, cellular iron levels and intracellular calcium. Further, studies have found that NDRG1 is up-regulated in neoplastic cells after treatment with novel iron chelators, which are a promising therapy for effective cancer management. Although the pathways by which NDRG1 exerts its functions in cancers have been documented, the relationship between the molecular structure of this protein and its functions remains unclear. In fact, recent studies suggest that, in certain cancers, NDRG1 is post-translationally modified, possibly by the activity of endogenous trypsins, leading to a subsequent alteration in its metastasis suppressor activity. This review describes the role of this important metastasis suppressor and discusses interesting unresolved issues regarding this protein.
Pub.: 26 Nov '13, Pinned: 31 Aug '17
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