title: NDRG2 inhibits hepatocellular carcinoma adhesion, migration and invasion by regulating CD24 expression.
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.
authors.affiliation: State Key Discipline of Cell Biology, Department of Oncology, Xijing Hospital, The Fourth Military Medical University, Xi'an, 710032, China.
authors.forename: Jin
authors.initials: J
authors.lastname: Zheng
authors.forename: Yan
authors.initials: Y
authors.lastname: Li
authors.forename: Jiandong
authors.initials: J
authors.lastname: Yang
authors.forename: Qiang
authors.initials: Q
authors.lastname: Liu
authors.forename: Ming
authors.initials: M
authors.lastname: Shi
authors.forename: Rui
authors.initials: R
authors.lastname: Zhang
authors.forename: Hengjun
authors.initials: H
authors.lastname: Shi
authors.forename: Qinyou
authors.initials: Q
authors.lastname: Ren
authors.forename: Ji
authors.initials: J
authors.lastname: Ma
authors.forename: Hang
authors.initials: H
authors.lastname: Guo
authors.forename: Yurong
authors.initials: Y
authors.lastname: Tao
authors.forename: Yan
authors.initials: Y
authors.lastname: Xue
authors.forename: Ning
authors.initials: N
authors.lastname: Jiang
authors.forename: Libo
authors.initials: L
authors.lastname: Yao
authors.forename: Wenchao
authors.initials: W
authors.lastname: Liu
mesh_terms: D051927:CD24 Antigen / Q000235:genetics / Q000378:metabolism*; D006528:Carcinoma, Hepatocellular / Q000235:genetics / Q000473:pathology*; D002448:Cell Adhesion; D045744:Cell Line, Tumor; D002465:Cell Movement; D015972:Gene Expression Regulation, Neoplastic; D022781:Hepatocytes / Q000378:metabolism; D006801:Humans; D008113:Liver Neoplasms / Q000235:genetics / Q000473:pathology*; D025521:Tumor Suppressor Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: D051927:CD24 Antigen; C466228:NDRG2 protein, human; D025521:Tumor Suppressor Proteins