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Open Access Research article

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

Jin Zheng16, Yan Li2, Jiandong Yang3, Qiang Liu4, Ming Shi5, Rui Zhang2, Hengjun Shi6, Qinyou Ren6, Ji Ma1, Hang Guo1, Yurong Tao1, Yan Xue1, Ning Jiang1, Libo Yao2* and Wenchao Liu1*

Author Affiliations

1 State Key Discipline of Cell Biology, Department of Oncology, Xijing Hospital, The Fourth Military Medical University, Xi'an, 710032, China

2 Department of Biochemistry and Molecular Biology, The State Key Laboratory of Cancer Biology, The Fourth Military Medical University, Xi'an, 710032, China

3 Department of Hepatobiliary Surgery, Xijing Hospital, The Fourth Military Medical University, Xi'an, 710032, China

4 Department of Hematology, Tangdu Hospital, The Fourth Military Medical University, Xi'an, 710038, China

5 Department of Neurology, Xijing Hospital, The Fourth Military Medical University, Xi'an, 710032, China

6 Department of Traditional Chinese and Western Medicine of Oncology, Tangdu Hospital, The Fourth Military Medical University, Xi'an, 710038, China

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BMC Cancer 2011, 11:251  doi:10.1186/1471-2407-11-251

Published: 16 June 2011

Abstract

Background

The 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.

Methods

The 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.

Results

NDRG2 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).

Conclusions

Our 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.