title: End-binding protein 1 stimulates paclitaxel sensitivity in breast cancer by promoting its actions toward microtubule assembly and stability.
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.
authors.affiliation: State Key Laboratory of Medicinal Chemical Biology, College of Life Sciences, Nankai University, Tianjin, 300071, China.
authors.forename: Youguang
authors.initials: Y
authors.lastname: Luo
authors.forename: Dengwen
authors.initials: D
authors.lastname: Li
authors.forename: Jie
authors.initials: J
authors.lastname: Ran
authors.forename: Bing
authors.initials: B
authors.lastname: Yan
authors.forename: Jie
authors.initials: J
authors.lastname: Chen
authors.forename: Xin
authors.initials: X
authors.lastname: Dong
authors.forename: Zhu
authors.initials: Z
authors.lastname: Liu
authors.forename: Ruming
authors.initials: R
authors.lastname: Liu
authors.forename: Jun
authors.initials: J
authors.lastname: Zhou
authors.forename: Min
authors.initials: M
authors.lastname: Liu
mesh_terms: D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology* / Q000627:therapeutic use; D017209:Apoptosis / Q000187:drug effects*; D001943:Breast Neoplasms / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology*; D059447:Cell Cycle Checkpoints / Q000187:drug effects; D045744:Cell Line, Tumor; D005260:Female; D006801:Humans; D061986:MCF-7 Cells; D008869:Microtubule-Associated Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D008870:Microtubules / Q000737:chemistry / Q000378:metabolism*; D017239:Paclitaxel / Q000494:pharmacology* / Q000627:therapeutic use; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000378:metabolism
chemical_list: D000972:Antineoplastic Agents, Phytogenic; C500985:MAPRE1 protein, human; D008869:Microtubule-Associated Proteins; D034741:RNA, Small Interfering; D017239:Paclitaxel
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