Hypoxic stress has been shown to induce NDRG1 expression in a variety of cells, but NDRG1’s roles during hypoxia are not fully understood. We identified a similar expression pattern of only seven genes, including NDRG1, when comparing the global gene expression profile in ZR-75-1 cells grown under hypoxia with cells ectopically over-expressing NDRG1. Thus, NDRG1 does not act as a sensor of intracellular oxygen tension. The elevated NDRG1 expression is rather a secondary effect of hypoxic stress. NDRG1 is induced both by ectopically expressed and endogenously increased TP53, the NDRG1 promoter contains a putative TP53 binding site. In line with this, we detected decreased apoptosis in doxorubicin-treated breast epithelial cells expressing NDRG1 shRNAs under normoxia. Other studies show no correlation between NDRG1 expression and apoptosis despite the up-regulation of TP53, suggesting different responses depending on the cell types and conditions studied. Jung et al. demonstrated that hypoxia-induced NDRG1 expression can mediate doxorubicin resistance, suggesting that NDRG1 might increase cellular survival under hypoxia. We observed strongly elevated NDRG1 levels under hypoxia and in cells subjected to acute DNA-damage by doxorubicin treatment. Under hypoxia we detected an even cytoplasmic NDRG1 signal, whereas doxorubicin treatment resulted in a granulated signal. NDRG1 did not co-localize with ER or early endosomes under the conditions tested. Our results are consistent with the report by Shi et al., who detected NDRG1 at the cell membrane and the cytoplasmic network closely associated with the ER in trophoblasts under hypoxia. Our observations are in agreement with NDRG1 exerting its functions through different stress-signalling pathways, resulting in increased cell survival under hypoxia, while being permissive for doxorubicin-induced apoptosis under normoxic conditions. In cells over-expressing NDRG1, the levels of CDC42EP, DOCK11 and ARHGEF1 detected on the micro arrays are shifted in a direction that is in agreement with an induction of increased CDC42 activity, conceivably resulting in increased vesicle trafficking. Thus, NDRG1 may indirectly play a role in vesicle trafficking and in maintenance of cellular polarity, by stimulating CDC42. Interestingly, hyperactivation of CDC42 can contribute to cellular transformation and tumor invasion and metastasis, through generation of plasma membrane protrusions, so-called invadopodia. Further investigations are needed to clarify the putative interplay between NDRG1 and CDC42 signalling pathways. In humans, Alaskan ICI 182780 Estrogen Receptor inhibitor Malamute and Greyhound, germline NDRG1 mutations cause the demyelinating disorder CMT4D and Ndrg1 deficient mice show defects connected to myelin sheath maintenance. Generally, many genes affected in Charcot-Marie-Tooth disease include proteins involved in regulation of endocytosis and vesicle transport. In a study of an early onset demyelinating disease, classified as CMT4H in one Lebanese and one Algerian family, Delague and colleagues identified novel mutations in a protein directly influencing the activity of CDC.