Microtubule-binding protein CLIP-170 is a mediator of 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.
Authors	Xiaodong Sun, Dengwen Li, Yunfan Yang, Yuan Ren, Jingyu Li, Zaizhu Wang, Bin Dong, Min Liu, Jun Zhou
Journal	The Journal of pathology (J Pathol) Vol. 226 Issue 4 Pg. 666-73 (Mar 2012) ISSN: 1096-9896 [Electronic] England
PMID	21989536 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Copyright	Copyright © 2012 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
Chemical References	Antineoplastic Agents, Phytogenic Microtubule-Associated Proteins Neoplasm Proteins cytoplasmic linker protein 170 Paclitaxel
Topics	Antineoplastic Agents, Phytogenic (pharmacology) Antineoplastic Combined Chemotherapy Protocols (therapeutic use) Breast Neoplasms (drug therapy, metabolism, surgery) Cell Line, Tumor Cell Proliferation (drug effects) Drug Screening Assays, Antitumor Female Humans Microtubule-Associated Proteins (metabolism) Microtubules (drug effects, metabolism) Neoadjuvant Therapy Neoplasm Proteins (metabolism) Paclitaxel (pharmacology)

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