Downregulation of NDRG1 promotes invasion of human gastric cancer AGS cells through MMP-2.

The N-myc downstream-regulated gene-1 (NDRG1) has recently been proposed as a metastasis suppressor, but its precise role remains unclear. To investigate whether NDRG1 can indeed influence the metastasis progress, expression of endogenous NDRG1 was knocked down in human AGS gastric adenocarcinoma cells using RNA interference. Stable NDRG1 "silenced" transfectants showed similar growth rates as their control counterparts. By contrast, invasive ability in Matrigel invasion activity and Gelatinolytic activity by matrix metalloproteinase-2 (MMP-2) were markedly increased in NDRG1 "silenced" cells. Moreover, re-expression of NDRG1 by recombinant adenovirus Ad-NDRG1 in NDRG1 "silenced" cells inhibited the increased invasive ability. Further study, we found the induction of MMP-2 by downregulation of NDRG1 was mediated by MT1-MMP. Altogether, our results imply that NDRG-1 could play a key role in the regulation of cellular invasion and metastasis, which may involve the upregulation of matrix metalloproteinases.