EFEMP1 inhibits migration of hepatocellular carcinoma by regulating MMP2 and MMP9 via ERK1/2 activity.
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).
Department of Hepatology, Qilu Hospital of Shandong University, Jinan, Shandong 250012, P.R. China.
Cheng-Yun
CY
Dou
Department of Pathology, The First Afﬁliated Hospital, Sun Yat-Sen University, Guangzhou, Guangdong 510080, P.R. China.
Chuang-Jie
CJ
Cao
Department of Pathology, The First Afﬁliated Hospital, Sun Yat-Sen University, Guangzhou, Guangdong 510080, P.R. China.
Zhuo
Z
Wang
Department of Experimental Research, Sun Yat-Sen University Cancer Center, Guangzhou, Guangdong 510080, P.R. China.
Ru-Hua
RH
Zhang
Department of Experimental Research, Sun Yat-Sen University Cancer Center, Guangzhou, Guangdong 510080, P.R. China.
Lei-Lei
LL
Huang
Department of Pathology, The First Afﬁliated Hospital, Sun Yat-Sen University, Guangzhou, Guangdong 510080, P.R. China.
Jia-Yan
JY
Lian
Department of Pathology, The First Afﬁliated Hospital, Sun Yat-Sen University, Guangzhou, Guangdong 510080, P.R. China.
Wen-Lin
WL
Xie
Department of Pathology, The First Afﬁliated Hospital, Sun Yat-Sen University, Guangzhou, Guangdong 510080, P.R. China.
Lian-Tang
LT
Wang
D002070:Butadienes / Q000494:pharmacology; D006528:Carcinoma, Hepatocellular / Q000235:genetics / Q000473:pathology*; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics*; D015536:Down-Regulation / Q000235:genetics; D016326:Extracellular Matrix Proteins / Q000235:genetics*; D048049:Extracellular Signal-Regulated MAP Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D015972:Gene Expression Regulation, Neoplastic; D056945:Hep G2 Cells; D006801:Humans; D007150:Immunohistochemistry; D008113:Liver Neoplasms / Q000235:genetics / Q000473:pathology*; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism*; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism*; D009570:Nitriles / Q000494:pharmacology; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D015398:Signal Transduction
D002070:Butadienes; C119630:EFEMP1 protein, human; D016326:Extracellular Matrix Proteins; D009570:Nitriles; D034741:RNA, Small Interfering; C113580:U 0126; D048049:Extracellular Signal-Regulated MAP Kinases; C522361:MMP2 protein, human; D020778:Matrix Metalloproteinase 2; C579270:MMP9 protein, human; D020780:Matrix Metalloproteinase 9