The Function of N-Myc Downstream-Regulated Gene 2 (NDRG2) as a Negative Regulator in Tumor Cell Metastasis

N-myc downstream-regulated gene 2 (NDRG2) is a tumor-suppressor gene that suppresses tumorigenesis and metastasis of tumors and increases sensitivity to anti-cancer drugs. In this review, we summarize information on the clinicopathological characteristics of tumor patients according to NDRG2 expression in various tumor tissues and provide information on the metastasis inhibition-related cell signaling modulation by NDRG2. Loss of NDRG2 expression is a prognostic factor that correlates with TNM grade and tumor metastasis and has an inverse relationship with patient survival in various tumor patients. NDRG2 inhibits cell signaling, such as AKT-, NF-kappa B-, STAT3-, and TGF-beta-mediated signaling, to induce tumor metastasis, and induces activation of GSK-3 beta which has anti-tumor effects. Although NDRG2 operates as an adaptor protein to mediate the interaction between kinases and phosphatases, which is essential in regulating cell signaling related to tumor metastasis, the molecular mechanism of NDRG2 as an adapter protein does not seem to be fully elucidated. This review aims to assist the research design regarding NDRG2 function as an adaptor protein and suggests NDRG2 as a molecular target to inhibit tumor metastasis and improve the prognosis in tumor patients.

Automated summary

N-myc downstream-regulated gene 2 (NDRG2) is a tumor-suppressor gene that inhibits tumorigenesis and metastasis of tumors. Loss of NDRG2 expression is associated with higher tumor grade, increased metastasis, and decreased patient survival. NDRG2 inhibits multiple cell signaling pathways involved in tumor metastasis and activates GSK-3 beta, which has anti-tumor effects. Although the molecular mechanism of NDRG2 as an adaptor protein is not fully understood, it holds potential as a molecular target for inhibiting tumor metastasis and improving patient prognosis.