title: Cyclophilin A promotes human hepatocellular carcinoma cell metastasis via regulation of MMP3 and MMP9.
abstract: Cyclophilin A (CypA) is a member of peptidyl prolyl isomerases (PPIases), which catalyze the cis/trans isomerization of prolyl peptide bonds on the NH-terminal side of Pro residues in peptide chains. Altered expression of CypA has been reported in hepatocellular carcinoma (HCC), but the biological functions of CypA in HCC remain unknown. We found that the level of CypA expression correlated with the metastatic capability of two HCC cell lines, MHCC97-L and MHCC97-H. Stable expression of ectopic CypA in SK-Hep1 cells promotes cell adhesion, motility, chemotaxis, and in vivo lung metastasis, without affecting cell proliferation. We further analyzed microarray results to identify target genes controlled by CypA. Twenty-one genes related to metastasis were altered by CypA over-expression. A member of matrix metalloproteinase, MMP3, was identified by microarray analysis. The regulation of MMP3 and its homologue MMP9 by CypA were further confirmed by quantitative real-time RT-PCR and zymography assay. Taken together, our data suggest that CypA promotes HCC cell metastasis at least partially through up-regulation of MMP3 and MMP9.
authors.affiliation: State Key Laboratory of Genetic Engineering, Institute of Genetics, School of Life Sciences, Fudan University, Shanghai 200433, People's Republic of China.
authors.forename: Mingjun
authors.initials: M
authors.lastname: Zhang
authors.forename: Chun
authors.initials: C
authors.lastname: Dai
authors.forename: Hengrui
authors.initials: H
authors.lastname: Zhu
authors.forename: Shuai
authors.initials: S
authors.lastname: Chen
authors.forename: Yanhua
authors.initials: Y
authors.lastname: Wu
authors.forename: Qiang
authors.initials: Q
authors.lastname: Li
authors.forename: Xianzhuo
authors.initials: X
authors.lastname: Zeng
authors.forename: Wenzhang
authors.initials: W
authors.lastname: Wang
authors.forename: Jie
authors.initials: J
authors.lastname: Zuo
authors.forename: Mei
authors.initials: M
authors.lastname: Zhou
authors.forename: Zongjun
authors.initials: Z
authors.lastname: Xia
authors.forename: Guoqing
authors.initials: G
authors.lastname: Ji
authors.forename: Hexige
authors.initials: H
authors.lastname: Saiyin
authors.forename: Lunxiu
authors.initials: L
authors.lastname: Qin
authors.forename: Long
authors.initials: L
authors.lastname: Yu
mesh_terms: D000818:Animals; D006528:Carcinoma, Hepatocellular / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D002448:Cell Adhesion / Q000235:genetics; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D021984:Cyclophilin A / Q000235:genetics / Q000378:metabolism*; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008113:Liver Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D019278:Matrix Metalloproteinase 3 / Q000235:genetics / Q000378:metabolism*; D020780:Matrix Metalloproteinase 9 / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008819:Mice, Nude; D046228:Microarray Analysis; D009361:Neoplasm Invasiveness / Q000235:genetics; D009362:Neoplasm Metastasis
chemical_list: C511768:MMP3 protein, human; D019278:Matrix Metalloproteinase 3; D020780:Matrix Metalloproteinase 9; D021984:Cyclophilin A