TY - JOUR
T1 - NEK2 Induces Drug Resistance Mainly through Activation of Efflux Drug Pumps and Is Associated with Poor Prognosis in Myeloma and Other Cancers
AU - Zhou, Wen
AU - Yang, Ye
AU - Xia, Jiliang
AU - Wang, He
AU - Salama, Mohamed E.
AU - Xiong, Wei
AU - Xu, Hongwei
AU - Shetty, Shashirekha
AU - Chen, Tiehua
AU - Zeng, Zhaoyang
AU - Shi, Lei
AU - Zangari, Maurizio
AU - Miles, Rodney
AU - Bearss, David
AU - Tricot, Guido
AU - Zhan, Fenghuang
N1 - Funding Information:
This work was supported by National Cancer Institute grants R01CA115399 (to G.T.), R01CA152105 (to F.Z.), and R21CA143887 (to F.Z.), the MMRF Senior (to F.Z., 2008 and 2010), the leukemia lymphoma society TRP (to F.Z., 2010 and 2011), and institutional start -up funds from the School of Medicine and Huntsman Cancer Institute of the University of Utah (to F.Z.).
PY - 2013/1/14
Y1 - 2013/1/14
N2 - Using sequential gene expression profiling (GEP) samples, we defined a major functional group related to drug resistance that contains chromosomal instability (CIN) genes. One CIN gene in particular, NEK2, was highly correlated with drug resistance, rapid relapse, and poor outcome in multiple cancers. Overexpressing NEK2 in cancer cells resulted in enhanced CIN, cell proliferation and drug resistance, while targeting NEK2 by NEK2 shRNA overcame cancer cell drug resistance and induced apoptosis in vitro and in a xenograft myeloma mouse model. High expression of NEK2 induced drug resistance mainly through activation of the efflux pumps. Thus, NEK2 represents a strong predictor for drug resistance and poor prognosis in cancer and could be an important target for cancer therapy.
AB - Using sequential gene expression profiling (GEP) samples, we defined a major functional group related to drug resistance that contains chromosomal instability (CIN) genes. One CIN gene in particular, NEK2, was highly correlated with drug resistance, rapid relapse, and poor outcome in multiple cancers. Overexpressing NEK2 in cancer cells resulted in enhanced CIN, cell proliferation and drug resistance, while targeting NEK2 by NEK2 shRNA overcame cancer cell drug resistance and induced apoptosis in vitro and in a xenograft myeloma mouse model. High expression of NEK2 induced drug resistance mainly through activation of the efflux pumps. Thus, NEK2 represents a strong predictor for drug resistance and poor prognosis in cancer and could be an important target for cancer therapy.
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U2 - 10.1016/j.ccr.2012.12.001
DO - 10.1016/j.ccr.2012.12.001
M3 - Article
C2 - 23328480
AN - SCOPUS:84872373803
SN - 1535-6108
VL - 23
SP - 48
EP - 62
JO - Cancer cell
JF - Cancer cell
IS - 1
ER -