N-myc downstream-regulated gene 1 protein (NDRG1) (NDRG1)

N-myc downstream-regulated gene 1 (NDRG1) is a 43 kDa protein belonging to the alpha/beta hydrolase superfamily, although it lacks a functional catalytic triad (UniProt: P55910). It is ubiquitously expressed but highly regulated by various stimuli, including hypoxia, cellular iron levels, and heavy metal exposure (PubMed: 22431510). NDRG1 plays a critical role in cellular differentiation, lipid metabolism, and the maintenance of myelin sheaths in the peripheral nervous system; notably, loss-of-function mutations in the NDRG1 gene are the primary cause of Charcot-Marie-Tooth disease type 4D (OMIM: 605262). In oncology, NDRG1 is widely recognized as a potent metastasis suppressor that inhibits multiple signaling pathways involved in epithelial-mesenchymal transition (EMT), such as the Wnt/beta-catenin, TGF-beta, and Ras/MAPK pathways (PubMed: 27448974). Therapeutic strategies often focus on inducing NDRG1 expression using novel iron chelators like Dp44mT and DpC, which have shown efficacy in preclinical models by sequestering intracellular iron and subsequently upregulating NDRG1 to inhibit tumor growth and spread (PubMed: 26912451).

Other names

CAP43Drg1RTPRit42TDD5Proxy-1GC4N-myc downstream-regulated gene 1

Upregulation of NDRG1 expression through intracellular iron chelation or hypoxia-mimetic pathways, which subsequently inhibits oncogenic signaling cascades including Wnt/beta-catenin, TGF-beta, and Ras/MAPK to suppress tumor growth and metastasis (PubMed: 27448974, PubMed: 26912451).