Calpains are required for invasive and metastatic potentials of human HCC cells

Authors

  • Bo Chen,

    1. Cell Engineering Research Centre and Department of Cell Biology, State Key Discipline of Cell Biology, Fourth Military Medical University, Xi'an 710032, China
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  • Juan Tang,

    1. Cell Engineering Research Centre and Department of Cell Biology, State Key Discipline of Cell Biology, Fourth Military Medical University, Xi'an 710032, China
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  • Yun-Shan Guo,

    1. Cell Engineering Research Centre and Department of Cell Biology, State Key Discipline of Cell Biology, Fourth Military Medical University, Xi'an 710032, China
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  • Yong Li,

    1. Cell Engineering Research Centre and Department of Cell Biology, State Key Discipline of Cell Biology, Fourth Military Medical University, Xi'an 710032, China
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  • Zhi-Nan Chen,

    Corresponding author
    • Cell Engineering Research Centre and Department of Cell Biology, State Key Discipline of Cell Biology, Fourth Military Medical University, Xi'an 710032, China
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  • Jian-Li Jiang

    Corresponding author
    • Cell Engineering Research Centre and Department of Cell Biology, State Key Discipline of Cell Biology, Fourth Military Medical University, Xi'an 710032, China
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  • Bo Chen and Juan Tang contributed equally to this work.

Corresponding authors: e-mail: jiangjl@fmmu.edu.cn (J.-L. Jiang); zhinanchen@fmmu.edu.cn (Z.-N. Chen)

Abstract

Calpains are a conserved family of calcium-dependent cysteine proteinases involved in various cellular functions. Two ubiquitous isoforms, µ- and m-calpain, are key members of the calpain family that play essential roles in regulating cell migration and invasion. However, it remains unclear whether they are involved in the progression of hepatocellular carcinoma (HCC). Here, we investigated the functions of µ- and m-calpain in the invasive and metastatic processes of human hepatoma cells. Our results indicated that the expression levels of calpains were elevated in HCC cells compared with those in normal hepatic cells. Our results indicated that small interfering RNA (siRNA)-mediated silencing of µ- and m-calpain expressions significantly suppressed the adhesive, migrative and invasive potentials of human hepatoma cells. The matrix metalloproteinases (MMPs) are key regulators of malignant tumour invasion and metastasis. siRNA-mediated down-regulation of µ- and m-calpain expressions also significantly attenuated MMP-2 and MMP-9 secretion. Thus µ- and m-calpain may play important roles in the invasion and metastasis of human hepatoma cells, and calpains may be drug targets for preventing HCC metastasis.

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