The role of NDRG1 in the pathology and potential treatment of human cancers

Abstract

N-myc downstream regulated gene 1 (NDRG1) has been well characterised to act as a metastatic suppressor in a number of human cancers. It has also been implicated to have a significant function in a number of physiological processes such as cellular differentiation and cell cycle. In this review, we discuss the role of NDRG1 in cancer pathology. NDRG1 was observed to be downregulated in the majority of cancers. Moreover, the expression of NDRG1 was found to be significantly lower in neoplastic tissues as compared with normal tissues. The most important function of NDRG1 in inhibiting tumour progression is associated with its ability to suppress metastasis. However, it has also been shown to have important effects on other stages of cancer progression (primary tumour growth and angiogenesis). Recently, novel iron chelators with selective antitumour activity (ie, Dp44mT, DpC) were shown to upregulate NDRG1 in cancer cells. Moreover, Dp44mT showed its antimetastatic potential only in cells expressing NDRG1, making this protein an important therapeutic target for cancer chemotherapy. This observation has led to increased interest in the examination of these novel anticancer agents.

The Cultural Divide: Exponential Growth in Classical 2D and Metabolic Equilibrium in 3D Environments

“…The N-myc downstream-regulated gene 1 protein (NDRG1) was present in 18.8 fold higher amounts in spheroids. NDRG1 has been shown to be a metastatic suppressor for several human cancers and has been implicated in several physiological processes including cellular differentiation and the G 0 /G 1 arrest [45]. Similarly, the ras GTPase-activating-like protein IQGAP2 was strongly increased (5.53).…”

The metastasis suppressor, NDRG1, modulates β-Catenin phosphorylation and nuclear translocation by mechanisms involving FRAT1 and PAK4

“…A variety of studies have shown the important role of NDRG1 in inhibiting cancer cell metastasis (Kovacevic and Richardson, 2006;Liu et al, 2011b;Chen et al, 2012;Liu et al, 2012b;Bae et al, 2013;Mao et al, 2013b;Sun et al, 2013a). However, complete understanding of its mechanism of action remains an important research goal.…”

“…This included an examination of FRAT1 expression (Hagen et al, 2006;MacDonald et al, 2009;Verheyen and Gottardi, 2010;Bae et al, 2013) and GSK3b phosphorylation (at Ser9 and Tyr216; Wu and Pan, 2010), and an assessment of the expression of CK1 (Stamos and Weis, 2013), PP1 (Stamos and Weis, 2013) and PP2A (Ikeda et al, 2000).…”

“…N-myc downstream-regulated gene 1 (NDRG1) is a ubiquitously expressed, predominantly cytosolic protein (Bae et al, 2013), which markedly reduces the metastasis of tumor cells in vivo, including those derived from prostate and colon cancers (Guan et al, 2000;Bandyopadhyay et al, 2003;Liu et al, 2012b). In fact, a variety of studies have revealed a negative correlation between NDRG1 expression and cancer grade and spread, indicating its role as a suppressor of metastasis (Fang et al, 2014).…”

Identification and functional characterization of two missense mutations in NDRG1 associated with Charcot‐Marie‐Tooth disease type 4D

“…To further characterize the functional effects of these two missense variants in NDRG1 , cell transfection studies were performed in this report. It is well known that NDRG1 is widely expressed in a variety of human tissues and was first regarded as a metastatic suppressor in a number of human cancers (Bae et al., ). NDRG1 is located in the cytoplasm and nucleus and is related to vesicle transport (Askautrud et al., ; Berger et al., ; Bucci, Bakke & Progida, ; King et al., ).…”