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

NDRG2 inhibits hepatocellular carcinoma adhesion, migration and invasion by regulating CD24 expression.
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NDRG2通过调节CD24表达抑制肝细胞癌粘附、迁移和侵袭

DOI:
10.1186/1471-2407-11-251
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发表时间:
2011-06-16
期刊:
影响因子:
3.8
通讯作者:
Liu W
Liu W
中科院分区:
医学2区
文献类型:
--
作者:
Zheng J;Li Y;Yang J;Liu Q;Shi M;Zhang R;Shi H;Ren Q;Ma J;Guo H;Tao Y;Xue Y;Jiang N;Yao L;Liu W

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背景肝细胞癌(HCC)转移率高,预后差。了解肝癌转移的分子机制是非常迫切的。CD 24和NDRG 2(N-myc downstream-regulated gene 2,N-myc downstream-regulated gene 2)在HCC中的作用尚不清楚。通过腺病毒或siRNA上调或下调NDRG 2来检测细胞粘附、迁移和侵袭的变化。采用免疫组化和Western blotting方法分析NDRG 2和CD 24在HCC组织中的表达模式及其与HCC临床特征的关系。NDRG 2通过调节CD 24发挥抗肿瘤活性,CD 24是介导细胞-细胞相互作用、肿瘤增殖和粘附的分子。NDRG 2上调可降低CD 24表达和细胞粘附、迁移和侵袭。相比之下,NDRG 2下调增强了CD 24表达以及细胞粘附、迁移和侵袭。免疫组化分析50例人肝癌临床标本显示NDRG 2下调和CD 24过表达之间有很强的相关性(P = 0.04)。此外,在AFP血清水平升高的患者中观察到NDRG 2下调频率增加(P = 0.006),晚期TNM分期(P = 0.009),分化差(P = 0.002),肿瘤浸润结论NDRG 2和CD 24在肝癌的粘附、迁移和侵袭中起重要作用。NDRG 2的表达水平与HCC的临床特征密切相关。因此,NDRG 2在HCC转移中起重要的生理作用。
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.
CD24是非小细胞肺癌患者中生存的独立预后标记。
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