Kinesin KIF4A is associated with chemotherapeutic drug resistance by regulating intracellular trafficking of lung resistance-related protein

作     者：Li-na PAN Yuan ZHANG Chang-jun ZHU Zhi-xiong DONG Li-na PAN;Yuan ZHANG;Chang-jun ZHU;Zhi-xiong DONG

作者机构：Tianjin Key Laboratory of Animal and Plant ResistanceCollege of Life SciencesTianjin Normal UniversityTianjin 300387China Key Laboratory of Molecular and Cellular Systems BiologyTianjin Normal UniversityTianjin 300387China Department of Cancer Research InstituteCancer Affiliated Hospital of Xinjiang Medical UniversityUrumqi 830000China 

出 版 物：《Journal of Zhejiang University-Science B(Biomedicine & Biotechnology)》 (浙江大学学报（英文版）B辑（生物医学与生物技术）)

年 卷 期：2017年第18卷第12期

页      面：1046-1054页

核心收录：

学科分类：0710[理学-生物学] 1007[医学-药学(可授医学、理学学位)] 1004[医学-公共卫生与预防医学(可授医学、理学学位)] 1002[医学-临床医学] 1001[医学-基础医学(可授医学、理学学位)] 0905[农学-畜牧学] 0906[农学-兽医学] 100214[医学-肿瘤学] 10[医学] 

基　　金：Project supported by the National Natural Science Foundation of China(Nos.31271485 and 31301138) the Tianjin Research Program of Application Foundation and Advanced Technology(No.12JC 2DJC21400) the Doctor Foundation of Tianjin Normal University(Nos.52XB1104 and 52XB1005) the Joint Funds of the Xinjiang Uygur Autonomous Region Natural Science Foundation(No.2016 D01C375) the Program for New Century Excellent Talents in University in China(No.NCET-11-1066) the State Key Laboratory of Molecular Oncology(No.SKL-KF-2017-18),China 

主　　题：KIF4A Lung resistance-related protein (LRP) Drug resistance 

摘      要：Multidrug resistance （MDR） is the major impediment to cancer chemotherapy. The expression of lung resistance-related protein （LRP）, a non-ATP-binding cassette （ABC） transporter, is high in tumor cells, resulting in their resistance to a variety of cytotoxic drugs. However, the function of LRP in tumor drug resistance is not yet explicit. Our previous studies had shown that Kinesin KIF4A was overexpressed in cisplatin （DDP）-resistant human lung adenocarcinoma cells （A549/DDP cells） compared with A549 cells. The expression of KIF4A in A549 or A549/DDP cells significantly affects cisplatin resistance but the detailed mechanisms remain unclear. Here, we performed co-immunoprecipitation experiments to show that the tail domain of KIF4A interacted with the N-terminal of LRP. Immunofluorescence images showed that both the ability of binding to LRP and the motility of KIF4A were essential for the dispersed cytoplasm distribution of LRP. Altogether, our results shed light on a potential mechanism in that motor protein KIF4A promotes drug resistance of lung adenocarcinoma cells through transporting LRP-based vaults along microtubules towards the cell membrane. Thus KIF4A might be a cisplatin resistance-associated protein and serves as a potential target for chemotherapeutic drug resistance in lung cancer.