Oncogenic but non-essential role of N-myc downstream regulated gene 1 in the progression of esophageal squamous cell carcinoma

Abstract

N-myc downstream regulated gene 1 (NDRG1/Cap43/Drg-1) has previously been shown to be dysregulated in esophageal squamous cell carcinoma (ESCC). In this study, we investigated the role of NDRG1 in the neoplastic progression of ESCC using ectopic gain-of-function and loss-of-function approaches. Stable transfectants of the KYSE30 ESCC cell line with altered NDRG1 levels were generated by lentiviral transduction. Although no measurable effects on in vitro cell proliferation were observed with altered NDRG1 expression, the ectopic overexpression of NDRG1 was positively linked to recognized markers of metastasis, angiogenesis and apoptotic evasion. Accordingly, in the nude mouse xenograft model system, NDRG1 overexpression promoted the in vivo growth of KYSE30 derived xenografts, which could be attributed to the reduced apoptotic and enhanced angiogenic activities associated with this gene. These processes were mediated in part by increased NFκB activity in NDRG1 overexpressing cells. Nevertheless, no significant phenotypic changes were observed in response to NDRG1 knock-down, suggesting that this gene might not be essential for the neoplastic progression of ESCC. Taken together, our results suggest that NDRG1 may play positive but dispensable roles in the progression of esophageal squamous cell carcinoma.

Canine Spontaneous Head and Neck Squamous Cell Carcinomas Represent Their Human Counterparts at the Molecular Level

“…Many known human HNSCC genes [ 1 , 2 , 47 – 49 ] are also amplified/deleted in the canine tumors. Examples include recurrent amplification of known oncogene MYC ; protein kinase genes MET , PTK2 (also known as FAK1 ) and FGFR1; apoptosis-related FADD; histone lysine methyltransferase gene WHSC1L1 ; NDRG1 (N-myc downstream regulated 1) which is frequently altered in human cancers including HNSCC but whose roles remain controversial [ 50 ]; cell cycle genes CCNE1 , CDK6 and E2F3 ; and others listed in S1E Table .…”

NDRG1 overexpression promotes the progression of esophageal squamous cell carcinoma through modulating Wnt signaling pathway

“…N-myc downregulated-gene 1 ( NDRG1 ) is a member of the NDRG family, which consists of 4 members in mammals, NDRG1, NDRG2, NDRG3 and NDRG4 . 1 The NDRG1 gene is approximately 60 kb in length and is located on chromosome 8q24.3. Its protein is composed of 394 amino acids and is highly conserved, with a molecular weight of 43 kDa.…”

“…25 It has also been reported that the ectopic overexpression of NDRG1 is highly associated with markers of metastasis, angiogenesis, apoptotic evasion, and enhanced NF-κB activity, suggesting that NDRG1 may play important roles in the progression of ESCC. 1 Ureshino et al. demonstrated that higher expression of NDRG1 is closely correlated with poor prognosis in gastric cancer patients and promotes the metastasis of gastric cancer via the epithelial-mesenchymal transition (EMT).…”

GR, Sgk1, and NDRG1 in esophageal squamous cell carcinoma: their correlation with therapeutic outcome of neoadjuvant chemotherapy

“…Factors including Sgk1 have also been considered as the cause of decreased sensitivity of cytotoxic drug therapy by activating the GC-GR pathway in hepatocellular carcinoma and colon adenocarcinoma [39]. Besides, GR-mediated Sgk1 activation suppressed tumor cell apoptosis in breast carcinoma cells [40] and NDRG1 was reported to be induced by Sgk1 to inhibit apoptosis in ESCC tumor cells [41]. These results above, as well as those from our present study, did indicate that the GR-Sgk1-NDRG1 pathway in ESCC could protect tumor cells from chemotherapyinduced apoptosis and mediate chemotherapy resistance.…”