NDRG2 inhibits hepatocellular carcinoma adhesion, migration and invasion by regulating CD24 expression

Abstract

BackgroundThe prognosis of most hepatocellular carcinoma (HCC) patients is poor due to the high metastatic rate of the disease. Understanding the molecular mechanisms underlying HCC metastasis is extremely urgent. The role of CD24 and NDRG2 (N-myc downstream-regulated gene 2), a candidate tumor suppressor gene, has not yet been explored in HCC.MethodsThe mRNA and protein expression of CD24 and NDRG2 was analyzed in MHCC97H, Huh7 and L-02 cells. Changes in cell adhesion, migration and invasion were detected by up- or down-regulating NDRG2 by adenovirus or siRNA. The expression pattern of NDRG2 and CD24 in HCC tissues and the relationship between NDRG2 and HCC clinical features was analyzed by immunohistochemical and western blotting analysis.ResultsNDRG2 expression was negatively correlated with malignancy in HCC. NDRG2 exerted anti-tumor activity by regulating CD24, a molecule that mediates cell-cell interaction, tumor proliferation and adhesion. NDRG2 up-regulation decreased CD24 expression and cell adhesion, migration and invasion. By contrast, NDRG2 down-regulation enhanced CD24 expression and cell adhesion, migration and invasion. Immunohistochemical analysis of 50 human HCC clinical specimens showed a strong correlation between NDRG2 down-regulation and CD24 overexpression (P = 0.04). In addition, increased frequency of NDRG2 down-regulation was observed in patients with elevated AFP serum level (P = 0.006), late TNM stage (P = 0.009), poor differentiation grade (P = 0.002), tumor invasion (P = 0.004) and recurrence (P = 0.024).ConclusionsOur findings indicate that NDRG2 and CD24 regulate HCC adhesion, migration and invasion. The expression level of NDRG2 is closely related to the clinical features of HCC. Thus, NDRG2 plays an important physiological role in HCC metastasis.

NDRG2 acts as a negative regulator downstream of androgen receptor and inhibits the growth of androgen-dependent and castration-resistant prostate cancer

“…[7][8][9][10][11] AR can promote ligand-independent prostate cancer progression by directly regulating the transcription of c-Myc, 30 which confers androgen independence. 29 As a target gene of c-Myc, 17 NDRG2 has been widely accepted as a tumor suppressor in many types of cancers, 15,21,[25][26][27] and our previous study reported a negative correlation between the expression of NDRG2 and that of c-Myc in prostate cancer. 27 These findings prompted us to investigate whether NDRG2 is involved in AR signaling and plays an important role in CRPC.…”

“…21 NDRG2 in particular has been proposed as a tumor suppressor 21 because mounting evidence demonstrates that NDRG2 is deregulated in various carcinomas, including glioblastoma, 15 breast cancer, 22 hepatocellular cancer 23 and colorectal cancer, 24 while upregulating NDRG2 could reverse the malignant phenotype of cancer cells. 21,25,26 Our most recent studies showed that NDRG2 expression levels were lower in PC tissues than in their benign counterparts, and forced expression of NDRG2 inhibited the proliferation and invasion of PC cells. 27,28 Particularly, NDRG2 inhibited proliferation of PC cell line PC3 by affecting several cell cycle regulators (cyclin-D1, CDK4 and p21), 27 supporting that NDRG2 plays a tumor suppressive role in PC.…”

Pancreatic Ductal Adenocarcinoma Stem Cells

“…CD24 is a mucin-like cell surface glycoprotein that has been identified in a variety of cancers including breast [26], liver [27], ovarian [28] and PDAC [14]. It is involved in cell adhesion and metastasis [29].…”

Corrigendum

“…The wound-healing method was carried out as described previously. 25 In brief, SW620 cells were wounded by scratching with a sterile pipette tip lengthwise along the chamber and were washed with PBS and cultured at 37 C for 1 day. After cell wounding for 0 h and 24 h, images were captured promptly, and OpenLab software was used to detect the wound width (mm).…”