がんの科学と治療

N-myc Downstream Regulated Gene (NDRG): Role in Cancer Metastasis Suppression and as Drug Target in Cancer Therapeutics

Abstract

Bekesho Geleta, Eyasu Makonnen and Solomon M Abay

N-myc downstream regulated gene (NDRG) is, a ubiquitously expressed, a family of cytosolic proteins consists of four members, NDRG1-4. It plays and important role in cancer such as aberrant expression, tumor suppressive, metastatic suppressive and oncogenic functions. In this review, we comprehensively present the expression as well as the clinical and pathological significance of NDRG in human cancers. NDRG1 one of NDRG family which is a ubiquitously expressed protein localized in different tissues of the body, especially breast. It may act as a central regulator of multiple signaling pathways that modulate tumor progression. NDRG2 is expressed in brain, gastric, pancreatic and prostate cells. NDRG3 is highly expressed in testis, prostate, muscle and ovary. Whereas, NDRG4 is highly expressed in brain, hear and colorectal cells. NDRG is down-regulated and associated with the incidence, progression and prognosis of diverse cancers. It is associated with tumor incidence, progression, and metastasis. NDRG has low expression in cancer patients, whereas, inducement of NDRG activity has metastatic suppression effect and also increased in apoptotic effect through increased p53 activity. Metastasis is the spread of a cancer from one organ or part of the body to another not directly connected with it. NDRG is negatively correlated with tumor progression in multiple neoplasms, being a promising new target for cancer treatment. Hence, a drug that has a capacity to enhance an activity of NDRG has a potential to be considered as anti-metastatic agent.