N-myc downstream-regulated gene 1 (NDRG1)

N-myc downstream-regulated gene 1 (NDRG1) is a 43 kDa protein belonging to the NDRG family and the alpha/beta hydrolase superfamily, although it lacks catalytic activity due to an inactive hydrolase motif. It is widely recognized as a potent metastasis suppressor that is transcriptionally repressed by N-myc and c-myc oncogenes and induced by cellular stress, including hypoxia and iron depletion. NDRG1 exerts its anti-tumor effects by inhibiting several key oncogenic pathways, such as EGFR, Wnt/beta-catenin, PI3K/AKT, and Ras signaling, often by promoting the degradation of receptors or stabilizing tumor suppressors like MIG6. Beyond its role in oncology, NDRG1 is essential for the maintenance of the myelin sheath in Schwann cells, and its mutation is the primary cause of Charcot-Marie-Tooth disease type 4D. In clinical settings, NDRG1 expression and its subcellular localization serve as important biomarkers for prognosis and metastatic potential in various cancers. Therapeutic strategies focusing on NDRG1 involve the use of iron-chelating agents, such as thiosemicarbazones (e.g., Dp44mT and DpC), which upregulate its expression to inhibit tumor growth and metastasis.

Other names

Drg1Cap43RTPRit42PROXY-1TDD5

Pharmacological induction of NDRG1 expression through iron chelation and HIF-1alpha activation, leading to the inhibition of multiple oncogenic signaling pathways including EGFR, Wnt/beta-catenin, and PI3K/AKT.