HAb18G/CD147 promotes cell motility by regulating annexin II-activated RhoA and Rac1 signaling pathways in hepatocellular carcinoma cells

Authors

  • Pu Zhao,

    1. Cell Engineering Research Center and Department of Cell Biology, State Key Laboratory of Cancer Biology, National Key Discipline of Cell Biology, Fourth Military Medical University, Xi'an, P.R. China
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    • *These authors contributed equally to this work.

  • Wei Zhang,

    1. General Hospital of Shenyang Military Region, Shenyang, P.R. China
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    • *These authors contributed equally to this work.

  • Shi-Jie Wang,

    1. Cell Engineering Research Center and Department of Cell Biology, State Key Laboratory of Cancer Biology, National Key Discipline of Cell Biology, Fourth Military Medical University, Xi'an, P.R. China
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    • *These authors contributed equally to this work.

  • Xiao-Ling Yu,

    1. Cell Engineering Research Center and Department of Cell Biology, State Key Laboratory of Cancer Biology, National Key Discipline of Cell Biology, Fourth Military Medical University, Xi'an, P.R. China
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  • Juan Tang,

    1. Cell Engineering Research Center and Department of Cell Biology, State Key Laboratory of Cancer Biology, National Key Discipline of Cell Biology, Fourth Military Medical University, Xi'an, P.R. China
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  • Wan Huang,

    1. Cell Engineering Research Center and Department of Cell Biology, State Key Laboratory of Cancer Biology, National Key Discipline of Cell Biology, Fourth Military Medical University, Xi'an, P.R. China
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  • Yong Li,

    1. Cell Engineering Research Center and Department of Cell Biology, State Key Laboratory of Cancer Biology, National Key Discipline of Cell Biology, Fourth Military Medical University, Xi'an, P.R. China
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  • Hong-Yong Cui,

    1. Cell Engineering Research Center and Department of Cell Biology, State Key Laboratory of Cancer Biology, National Key Discipline of Cell Biology, Fourth Military Medical University, Xi'an, P.R. China
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  • Yun-Shan Guo,

    1. Cell Engineering Research Center and Department of Cell Biology, State Key Laboratory of Cancer Biology, National Key Discipline of Cell Biology, Fourth Military Medical University, Xi'an, P.R. China
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  • Jan Tavernier,

    1. Flanders Interuniversity Institute for Biotechnology, Department of Medical Protein Research, Faculty of Medicine and Health Sciences, Ghent University, Ghent, Belgium
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  • Si-He Zhang,

    Corresponding author
    1. Cell Engineering Research Center and Department of Cell Biology, State Key Laboratory of Cancer Biology, National Key Discipline of Cell Biology, Fourth Military Medical University, Xi'an, P.R. China
    • Cell Engineering Research Centre & Department of Cell Biology, State Key Laboratory of Cancer Biology, Fourth Military Medical University, 17 West Changle Street, Xi'an 710032, China
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  • Jian-Li Jiang,

    Corresponding author
    1. Cell Engineering Research Center and Department of Cell Biology, State Key Laboratory of Cancer Biology, National Key Discipline of Cell Biology, Fourth Military Medical University, Xi'an, P.R. China
    • Cell Engineering Research Centre & Department of Cell Biology, State Key Laboratory of Cancer Biology, Fourth Military Medical University, 17 West Changle Street, Xi'an 710032, China
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    • fax: 86-29-83226349

  • Zhi-Nan Chen

    Corresponding author
    1. Cell Engineering Research Center and Department of Cell Biology, State Key Laboratory of Cancer Biology, National Key Discipline of Cell Biology, Fourth Military Medical University, Xi'an, P.R. China
    • Cell Engineering Research Centre & Department of Cell Biology, State Key Laboratory of Cancer Biology, Fourth Military Medical University, 17 West Changle Street, Xi'an 710032, China
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  • Potential conflict of interest: Nothing to report.

  • Supported by grants from the National Basic Research Program of China (2009CB521704), the National S&T Major Project (2008ZX10002-026), and the National Natural Science Foundation of China (81071691, 30970564, and 30800573).

Abstract

Tumor cells can move as individual cells in two interconvertible modes: mesenchymal mode and amoeboid mode. Cytoskeleton rearrangement plays an important role in the interconversion. Previously, we reported that HAb18G/CD147 and annexin II are interacting proteins involved in cytoskeleton rearrangement, yet the role of their interaction is unclear. In this study we found that the depletion of HAb18G/CD147 produced a rounded morphology, which is associated with amoeboid movement, whereas the depletion of annexin II resulted in an elongated morphology, which is associated with mesenchymal movement. The extracellular portion of HAb18G/CD147 can interact with a phosphorylation-inactive mutant of annexin II and inhibit its phosphorylation. HAb18G/CD147 inhibits Rho signaling pathways and amoeboid movement by inhibiting annexin II phosphorylation, promotes membrane localization of WAVE2 and Rac1 activation by way of the integrin-FAK-PI3K/PIP3 signaling pathway, and promotes the formation of lamellipodia and mesenchymal movement. Conclusion: These results suggest that the interaction of HAb18G/CD147 with annexin II is involved in the interconversion between mesenchymal and amoeboid movement of hepatocellular carcinoma cells. (HEPATOLOGY 2011)

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