NDRG3 Promote Colorectal Cancer Metastasis Through Phosphorylation Of Src

Objection: Despite noticeable improvements in early diagnosis,CRC stillcauses a large number of deaths ascribed to metastatic events.Therefore,it is of urgent need to elucidate the molecular mechanism that involved in the progression of CRC for early detection and target treatment.Recently,the N-myc down-regulated gene(NDRG)family has been discovered,which is involved in cell proliferation and differentiation.The aim of this article is to identify the role of NDRG3 in colorectal cancer(CRC)and to clarify the mechanism underlying its function.Methods: To investigate the NDRG3 expression in colorectal cancer tissues,q RT-PCR and immunohistochemistry staining were performed on 170 tumor and matched non-tumor tissues.We analyzed the relationship between the NDRG3 expression and the clinicopathological features.In order to explore the functions of NDRG3 in CRC cell lines,we generated a SW1116 cell line ectopically overexpressing NDRG3 and applied lentivirus-mediated sh RNA to knock down NDRG3 in RKO.The effect of overexpression and knockdown was determined by western blotting.To investigate the effect of NDRG3 expression on CRC growth,we examined the in vitro cell growth rates by CCK-8 and colony formation assays.Wound healing assay was used to evaluate the influences of NDRG3 on cellular migration.Transwell assays were performed to further detect the influences of NDRG3 on cellular migration and invasion.To determine the function of NDRG3 in the liver metastasis,we applied the portal vein injection model.Results: NDRG3 transcript levels were significantly increased in CRC samples compared to normal tissues(p < 0.01).Further,a correlation analysis between NDRG3 expression and the clinicopathological features revealed that the expression of NDRG3 in the CRC tissues was significantly related to invasion depth(p= 0.013),and TNM stage(p= 0.015).Overexpression of NDRG3 increased the proliferation rate of the SW1116 cells,while depletion of NDRG3 reduced the proliferation rate of the RKO cells,the experiment in vivo verified the vitro results.A longer distance was noticed in NDRG3 knockdown cells RKO when compared with the negative control cells.Wound healing assay and Transwell assays were performed to evaluate the influences of NDRG3 on cellular migration.the distance between wound edges of SW1116/NDRG3 cells was markedly shorter than those of SW1116/Vector cells.In contrast,a longer distance was noticed in NDRG3 knockdown cells RKO when compared with the negative control cells.Conclusion: NDRG3 was high expressed in colorectal cancer tissues,Our data showed that NDRG3 promotes CRC cell proliferation,migration and invasion,suggesting that NDRG3 may be an oncogene in CRC.