Considering the role of proto-oncogene c-Met (c-Met) in oncogenesis, we examined the effects of the metastasis suppressor, N-myc downstream regulated gene-1 (NDRG1), and two NDRG1-inducing thiosemicarbazone-based agents, Dp44mT and DpC, on c-Met expression in DU145 and Huh7 cells.
Our study could fulfill potential mechanisms of the NDRG1 during tumorigenesis and metastasis, which may serve as a tumor suppressor and potential target for new therapies in human colorectal cancer.
N-myc downstream regulated gene 1 (NDRG1) is an intriguing metastasis suppressor protein, which plays an important role in suppressing multiple oncogenic signaling pathways.
N-myc downstream regulated gene-1 (NDRG1) is a potent metastasis suppressor that is regulated by hypoxia, metal ions including iron, the free radical nitric oxide (NO<sup>.</sup>), and various stress stimuli.
The metastasis suppressor NDRG1 down-regulates the epidermal growth factor receptor via a lysosomal mechanism by up-regulating mitogen-inducible gene 6.
The metastasis suppressor, N-myc downstream-regulated gene-1 (NDRG1), plays multifaceted roles in inhibiting oncogenic signaling and can suppress the epithelial mesenchymal transition (EMT), a key step in metastasis.
Additionally, further studies show that the down-regulation of NDRG1 expression inhibited proliferation and metastasis of EC cells through the PTEN/AKT pathway.
Some of the genes upregulated by MP-HX include pro-apoptotic genes (DDIT3, BBC3, JUN), cell cycle arresting (CDKN1A, CDKN2B), growth arrest/repair (TP53, GADD45A) and metastasis suppression (NDRG1).
NDRG1 overexpression correlated with glycolytic and hypoxia-associated gene expression, and was associated with elevated rates of metastasis and patient mortality.
The metastasis suppressor, N-myc downstream regulated gene-1 (NDRG1), exhibits pleiotropic activity, inhibiting metastasis of various tumor-types, while being correlated with metastasis in others.
Therefore, our results revealed a role of NDR1 in the suppression of prostate cancer cell metastasis and provided a potential mechanism of action, thus offering new therapeutic strategies against prostate cancer metastasis.
In contrast, the metastasis suppressor N-myc downstream regulated gene 1 (NDRG1) has the opposite effect on the NF-<i>κ</i>B pathway, being able to inhibit NF-<i>κ</i>B activation and reduce angiogenesis, proliferation, migration, and cancer cell invasion.
In addition, caveolin-1 mediates the suppressive function of NDRG1 in epithelial-mesenchymal transition, migration and invasion in vitro and metastasis in vivo.
Here, we show that LSD1 affects motility and invasiveness of NB cells by modulating the transcription of the metastasis suppressor NDRG1 (N-Myc Downstream-Regulated Gene 1).
The current study is the first to elucidate a unique facet of the potent tumor/metastasis suppressor NDRG1 in the regulation of PDAC glycolysis, leading to important insights into the mechanism by which NDRG1 exert inhibitory function in PDAC.