NDRG1 suppresses vasculogenic mimicry and tumor aggressiveness in gastric carcinoma

Abstract

N-myc downstream regulated gene 1 (NDRG1) has been well characterized as a suppressor of metastasis in numerous types of carcinoma. NDRG1 inhibits the metastatic progression of cancer cells via its inhibitory effects on a wide variety of cellular signaling pathways. Vasculogenic mimicry (VM) refers to the unique ability of aggressive tumor cells to mimic the pattern of embryonic vasculogenic networks, and is the main reason for the poor prognosis and failure of antivascular therapy in gastric carcinoma (GC). Tumor cells can mimic the function of endothelial cells to exhibit VM through epithelial-mesenchymal transition (EMT). However, the potential function of NDRG1 in metastatic GC progression in patients has not yet been fully elucidated. To date, data regarding the function of NDRG1 in VM formation in GC have not been reported. The aim of the present study was to elucidate these unknown areas. To this end, 228 samples of human GC were used to identify the protein expression levels of NDRG1, VM-associated proteins and EMT-associated proteins via immunohistochemistry, and their clinical significance was assessed. In addition, the data of 415 patients with GC were collected from The Cancer Genome Atlas database. A functional enrichment analysis concerning NDRG1 was performed using Metascape and the Gene Set Enrichment Analysis (GSEA). In conclusion, the results of the present study indicate that NDRG1 is negatively correlated with poor prognosis through suppression of VM formation in GC. The results of the present study demonstrated that NDRG1 decreases EMT-associated protein expression and that HER2 expression may serve a significant role in this process. The Metascape and GSEA results also indirectly support this conclusion. The present study discusses the status NDRG1 as a prognostic and selective biomarker in GC, as well as current and future NDRG1-targeted therapies.

A comprehensive analysis of immune infiltration in the tumor microenvironment of osteosarcoma

“…MYCL is a promising treatment target for lung cancers 43 . NDRG1, a downstream regulatory gene of N‐myc, inhibits metastasis, and recurrence of tumors such as gastric cancer 44 . Over‐expression of B7‐H3 in colon cancer upregulates the B3GALT4 expression level.…”

“… 43 NDRG1, a downstream regulatory gene of N‐myc, inhibits metastasis, and recurrence of tumors such as gastric cancer. 44 Over‐expression of B7‐H3 in colon cancer upregulates the B3GALT4 expression level. Therefore, B3GALT4 is a potential prognostic and treatment target for colon cancer.…”

Hsa_circ_0003159 inhibits gastric cancer progression by regulating miR-223-3p/NDRG1 axis

“…Importantly, miR-223-3p has been reported to promote the development of GC by promoting cell proliferation, migration and invasion [15,16]. Moreover, N-myc downstream regulated gene 1 (NDRG1) is demonstrated as a metastasis suppressor and inhibit tumor malignancy of GC [17][18][19]. However, whether miR-223-3p and NDRG1 are associated with the mechanism of hsa_circ_0003159 is unknown.…”

Tenascin-c Knockdown Suppresses Vasculogenic Mimicry of Gastric Cancer by Inhibiting ERK- Triggered EMT

“…The cells were then xed with 4% paraformaldehyde and in ltrated with 0.3% Triton X-100. F-actin is an important pseudopodia component and is labeled with phalloidin labeled with Alexa Fluor 555 (A34055, Invitrogen, USA 6 ) in PBS were injected into the peritoneal cavity. The peritoneal metastasis was checked and recorded when the mice were sacri ced on the 14th day after injection.…”

“…Even the diagnosis and treatment of gastric cancer have improved these years, the prognosis of patients is still poor. Gastric cancer recurrence and metastasis remain the most common cause of poor long-term survival [6]. Tumor growth and metastasis require an adequate blood supply.…”