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

N-myc downstream regulated gene 1 (NDRG1) is a multifunctional protein primarily recognized for its potent activity as a metastasis suppressor in several solid tumors, including prostate, pancreatic, and colorectal cancers [4, 10, 11]. Although it belongs to the alpha/beta hydrolase superfamily, it lacks the necessary catalytic residues for enzymatic activity and instead functions as a scaffold and signaling regulator [5, 7, 12]. NDRG1 is induced by various stress stimuli, including hypoxia and iron depletion, and acts by inhibiting multiple oncogenic signaling cascades such as the Ras, Wnt/beta-catenin, and PI3K/AKT pathways [6, 11, 14]. In addition to its role in oncology, NDRG1 is essential for the maintenance of the myelin sheath in the peripheral nervous system; mutations in the NDRG1 gene are the primary cause of Charcot-Marie-Tooth disease type 4D [1, 5, 8]. Therapeutically, novel iron-chelating agents like thiosemicarbazones (e.g., DpC) are designed to upregulate NDRG1 expression to halt cancer progression and metastatic spread [9, 11]. Its expression profile and subcellular localization are increasingly being utilized as prognostic biomarkers to predict disease severity and treatment response in various malignancies [18, 19, 20].

Other names

CAP43Drg-1DRG1RTPTDD5Proxy-1GC4Rit42NDR1NMSLTARG1HMSNL

Upregulation of NDRG1 expression, often through iron chelation or stress induction, to inhibit multiple oncogenic pathways including Ras, PI3K/AKT, and Wnt/beta-catenin, while promoting the stabilization of tumor-suppressive proteins such as PTEN and E-cadherin.