EFEMP1 inhibits migration of hepatocellular carcinoma by regulating MMP2 and MMP9 via ERK1/2 activity
EFEMP1 inhibits migration of hepatocellular carcinoma by regulating MMP2 and MMP9 via ERK1/2 activity
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EFEMP1通过ERK1/2活性调节MMP2和MMP9抑制肝细胞癌的迁移
DOI：
10.3892/or.2016.4733
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发表时间：
2016-06-01
期刊：
影响因子：
4.2
通讯作者：
Wang, Lian-Tang
中科院分区：
文献类型：
--
作者：
Dou, Cheng-Yun;Cao, Chuang-Jie;Wang, Lian-Tang
含有表皮生长因子的纤维蛋白样细胞外基质蛋白 1 (EFEMP1) 抑制肝细胞癌 (HCC) 迁移的作用仍不清楚。通过蛋白质印迹和实时 PCR 定量 HCC 细胞系中 EFEMP1 的表达。通过 siRNA 并添加纯化的 EFEMP1 蛋白，在体外探索了 EFEMP1 在 HCC 细胞迁移中的作用。 EFEMP1下调后通过Western blotting检测相关分子的表达，并通过免疫组织化学检测。对 8 对 HCC 非 HCC 肝脏样本和 215 个 HCC 样本进行了免疫组织化学分析。 EFEMP1在7,721和HepG2 HCC细胞系中高表达，而HuH7 HCC细胞系与其他细胞系相比EFEMP1表达水平最低。通过siRNA下调EFEMP1显着增加了HCC细胞的迁移能力，而添加纯化的EFEMP1蛋白则抑制了HCC细胞的迁移。 EFEMP1 的下调会增加 ERK1/2、MMP2 和 MMP9 的表达。此外，U0126（一种高选择性和有效的pERK1/2抑制剂）可以消除siRNA增强的迁移能力。因此，通过免疫组织化学检测，MMP2和MMP9的表达与EFEMP1的表达呈反比。 EFEMP1在HCC组织中表达下调，且较低的EFEMP1表达与HCC患者腹水（P=0.050）、血管侵犯（P=0.044）、分化较差（P=0.002）和临床分期较高（P=0.003）显着相关。
The role of epidermal growth factor-containing fibulin-like extracellular matrix protein 1 (EFEMP1) inhibiting migration in hepatocellular carcinoma (HCC) remains unknown. Expression of EFEMP1 in HCC cell lines were quantified by western blotting and real-time PCR. The role of EFEMP1 in HCC cell migration was explored in vitro via siRNA and adding purified EFEMP1 protein. The associated molecule expression was detected by western blotting after downregulation of EFEMP1 and also tested by immunohistochemistry. Eight pairs of HCC non-HCC liver samples and 215 HCC samples were subjected to immunohistochemistry. EFEMP1 was highly expressed in 7,721 and HepG2 HCC cell lines while HuH7 HCC cell line expressed the lowest level of EFEMP1 compared with the others. Downregulating EFEMP1 by siRNA markedly increased the migration ability of HCC cells while adding purified EFEMP1 protein inhibited HCC cell migration. Downregulation of EFEMP1 increased the expression of ERK1/2, MMP2 and MMP9. Furthermore, U0126 (a highly selective and potent inhibitor of pERK1/2) could abrogate the migration ability enhanced by siRNA. Accordingly, MMP2 and MMP9 were inversely expressed with EFEMP1 expression by immunohistochemistry. EFEMP1 downregulated in HCC tissues, and lower EFEMP1 expression was significantly associated with HCC patients with ascites (P=0.050), vascular invasion (P=0.044), poorer differentiation (P=0.002) and higher clinical stage (P=0.003).