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Cyclophilin A promotes human hepatocellular carcinoma cell metastasis via regulation of MMP3 and MMP9

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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.

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Acknowledgments

We thank Prof. ZY Tang (Liver Cancer Institute & Zhongshan Hospital, Fudan University, Shanghai, P. R. China) for providing MHCC97-L and MHCC97-H cell lines. This work was supported by the National 973 program of China (2004CB518605), the National 863 project of China (2006AA020501), the National Key Sci-Tech Special Project of China (2008ZX10002-020), the Project of the Shanghai Municipal Science and Technology Commission (03dz14086), and the National Natural Science foundation of China (30024001, 30771188).

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Authors and Affiliations

  1. State Key Laboratory of Genetic Engineering, Institute of Genetics, School of Life Sciences, Fudan University, 220 Handan Road, Shanghai, 200433, People’s Republic of China

    Mingjun Zhang, Hengrui Zhu, Shuai Chen, Yanhua Wu, Qiang Li, Xianzhuo Zeng, Wenzhang Wang, Jie Zuo, Mei Zhou, Zongjun Xia, Guoqing Ji, Hexige Saiyin & Long Yu

  2. Liver Cancer Institute & Zhongshan Hospital, Institutes of Biomedical Science, Fudan University, Shanghai, 200433, People’s Republic of China

    Chun Dai & Lunxiu Qin

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  1. Mingjun Zhang
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  2. Chun Dai
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  15. Long Yu
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Correspondence to Long Yu.

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The first two authors contributed equally to this work.

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Zhang, M., Dai, C., Zhu, H. et al. Cyclophilin A promotes human hepatocellular carcinoma cell metastasis via regulation of MMP3 and MMP9. Mol Cell Biochem 357, 387–395 (2011). https://doi.org/10.1007/s11010-011-0909-z

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  • DOI: https://doi.org/10.1007/s11010-011-0909-z

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