Microtubule-binding protein CLIP-170 is a mediator of paclitaxel sensitivity

Authors

  • Xiaodong Sun,

    1. Department of Genetics and Cell Biology, Tianjin Key Laboratory of Protein Science, College of Life Sciences, Nankai University, Tianjin 300071, China
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    • These authors contributed equally to this work.

  • Dengwen Li,

    1. Department of Genetics and Cell Biology, Tianjin Key Laboratory of Protein Science, College of Life Sciences, Nankai University, Tianjin 300071, China
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    • These authors contributed equally to this work.

  • Yunfan Yang,

    1. Department of Genetics and Cell Biology, Tianjin Key Laboratory of Protein Science, College of Life Sciences, Nankai University, Tianjin 300071, China
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    • These authors contributed equally to this work.

  • Yuan Ren,

    1. Department of Genetics and Cell Biology, Tianjin Key Laboratory of Protein Science, College of Life Sciences, Nankai University, Tianjin 300071, China
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  • Jingyu Li,

    1. Department of Genetics and Cell Biology, Tianjin Key Laboratory of Protein Science, College of Life Sciences, Nankai University, Tianjin 300071, China
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  • Zaizhu Wang,

    1. Department of Genetics and Cell Biology, Tianjin Key Laboratory of Protein Science, College of Life Sciences, Nankai University, Tianjin 300071, China
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  • Bin Dong,

    1. Department of Genetics and Cell Biology, Tianjin Key Laboratory of Protein Science, College of Life Sciences, Nankai University, Tianjin 300071, China
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  • Min Liu,

    Corresponding author
    1. Department of Biochemistry, Key Laboratory of Immune Microenvironment and Disease of the Ministry of Education, Basic Medical College, Tianjin Medical University, Tianjin 300070, China
    • Department of Biochemistry, Key Laboratory of Immune Microenvironment and Disease of the Ministry of Education, Basic Medical College, Tianjin Medical University, Tianjin 300070, China.
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  • Jun Zhou

    Corresponding author
    1. Department of Genetics and Cell Biology, Tianjin Key Laboratory of Protein Science, College of Life Sciences, Nankai University, Tianjin 300071, China
    • Department of Genetics and Cell Biology, Tianjin Key Laboratory of Protein Science, College of Life Sciences, Nankai University, Tianjin 300071, China.
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  • No conflicts of interest were declared.

Abstract

CLIP-170 is a microtubule-binding protein and participates in diverse microtubule-associated cellular activities by regulating microtubule dynamics. Here we provide evidence that CLIP-170 is a mediator of the sensitivity of the anti-microtubule drug paclitaxel in breast cancer. In vitro cell proliferation assays reveal that CLIP-170 expression in breast cancer cell lines correlates with their sensitivity to paclitaxel. In addition, CLIP-170 expression in clinical samples of breast cancer correlates with the pathological response of tumours to paclitaxel-containing chemotherapy. Mitotic index and caspase-3 activity analyses reveal that CLIP-170 increases the abilities of paclitaxel to block cell cycle progression at mitosis and to induce apoptosis in breast cancer cells. By microtubule sedimentation assay and binding affinity analysis, we further find that CLIP-170 promotes paclitaxel binding to microtubules. In vitro tubulin polymerization assay shows that CLIP-170 enhances the activity of paclitaxel to promote microtubule assembly. These results demonstrate that CLIP-170 mediates paclitaxel sensitivity in breast cancer via a microtubule-dependent mechanism. Copyright © 2012 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

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