RESEARCH ARTICLE

End-binding protein 1 stimulates paclitaxel sensitivity in breast cancer by promoting its actions toward microtubule assembly and stability

  • Youguang Luo 1 ,
  • Dengwen Li 1 ,
  • Jie Ran 1 ,
  • Bing Yan 1 ,
  • Jie Chen 1 ,
  • Xin Dong 1 ,
  • Zhu Liu 2 ,
  • Ruming Liu 1 ,
  • Jun Zhou 1 ,
  • Min Liu , 2
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  • 1. State Key Laboratory of Medicinal Chemical Biology, College of Life Sciences, Nankai University, Tianjin 300071, China
  • 2. Tianjin Key Laboratory of Medical Epigenetics and Department of Biochemistry, School of Basic Medical Sciences, Tianjin

Received date: 09 Feb 2014

Accepted date: 09 Mar 2014

Published date: 26 Jun 2014

Copyright

2014 This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Abstract

Paclitaxel is a microtubule-targeting agent widely used for the treatment of many solid tumors. However, patients show variable sensitivity to this drug, and effective diagnostic tests predicting drug sensitivity remain to be investigated. Herein, we show that the expression of end-binding protein 1 (EB1), a regulator of microtubule dynamics involved in multiple cellular activities, in breast tumor tissues correlates with the pathological response of tumors to paclitaxel-based chemotherapy. In vitro cell proliferation assays reveal that EB1 stimulates paclitaxel sensitivity in breast cancer cell lines. Our data further demonstrate that EB1 increases the activity of paclitaxel to cause mitotic arrest and apoptosis in cancer cells. In addition, microtubule binding affinity analysis and polymerization/depolymerization assays show that EB1 enhances paclitaxel binding to microtubules and stimulates the ability of paclitaxel to promote microtubule assembly and stabilization. These findings thus reveal EB1 as a critical regulator of paclitaxel sensitivity and have important implications in breast cancer chemotherapy.

Cite this article

Youguang Luo , Dengwen Li , Jie Ran , Bing Yan , Jie Chen , Xin Dong , Zhu Liu , Ruming Liu , Jun Zhou , Min Liu . End-binding protein 1 stimulates paclitaxel sensitivity in breast cancer by promoting its actions toward microtubule assembly and stability[J]. Protein & Cell, 2014 , 5(6) : 469 -479 . DOI: 10.1007/s13238-014-0053-0

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