These authors contributed equally to this work.
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Original Paper
Microtubule-binding protein CLIP-170 is a mediator of paclitaxel sensitivity†
Article first published online: 17 JAN 2012
DOI: 10.1002/path.3026
Copyright © 2012 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
Additional Information
How to Cite
Sun, X., Li, D., Yang, Y., Ren, Y., Li, J., Wang, Z., Dong, B., Liu, M. and Zhou, J. (2012), Microtubule-binding protein CLIP-170 is a mediator of paclitaxel sensitivity. J. Pathol., 226: 666–673. doi: 10.1002/path.3026
- †
No conflicts of interest were declared.
- ‡
These authors contributed equally to this work.
Publication History
- Issue published online: 2 FEB 2012
- Article first published online: 17 JAN 2012
- Accepted manuscript online: 12 OCT 2011 05:25AM EST
- Manuscript Accepted: 30 SEP 2011
- Manuscript Revised: 27 SEP 2011
- Manuscript Received: 10 APR 2011
Keywords:
- CLIP-170;
- microtubule;
- breast cancer;
- paclitaxel;
- sensitivity
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.