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CLC number: Q291

On-line Access: 2017-12-05

Received: 2017-03-10

Revision Accepted: 2017-05-30

Crosschecked: 2017-11-15

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Journal of Zhejiang University SCIENCE B 2017 Vol.18 No.12 P.1046-1054


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

Author(s):  Li-na Pan, Yuan Zhang, Chang-jun Zhu, Zhi-xiong Dong

Affiliation(s):  Tianjin Key Laboratory of Animal and Plant Resistance, College of Life Sciences, Tianjin Normal University, Tianjin 300387, China; more

Corresponding email(s):   skydzx@tjnu.edu.cn

Key Words:  KIF4A, Lung resistance-related protein (LRP), Drug resistance

Li-na Pan, Yuan Zhang, Chang-jun Zhu, Zhi-xiong Dong. Kinesin KIF4A is associated with chemotherapeutic drug resistance by regulating intracellular trafficking of lung resistance-related protein[J]. Journal of Zhejiang University Science B, 2017, 18(12): 1046-1054.

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author="Li-na Pan, Yuan Zhang, Chang-jun Zhu, Zhi-xiong Dong",
journal="Journal of Zhejiang University Science B",
publisher="Zhejiang University Press & Springer",

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%T Kinesin KIF4A is associated with chemotherapeutic drug resistance by regulating intracellular trafficking of lung resistance-related protein
%A Li-na Pan
%A Yuan Zhang
%A Chang-jun Zhu
%A Zhi-xiong Dong
%J Journal of Zhejiang University SCIENCE B
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%I Zhejiang University Press & Springer
%DOI 10.1631/jzus.B1700129

T1 - Kinesin KIF4A is associated with chemotherapeutic drug resistance by regulating intracellular trafficking of lung resistance-related protein
A1 - Li-na Pan
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A1 - Chang-jun Zhu
A1 - Zhi-xiong Dong
J0 - Journal of Zhejiang University Science B
VL - 18
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SP - 1046
EP - 1054
%@ 1673-1581
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PB - Zhejiang University Press & Springer
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DOI - 10.1631/jzus.B1700129

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.




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[30]List of electronic supplementary materials

[31]Fig. S1 mRNA and protein expression of LRP and KIF4A in A549 and A549/DDP cells

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