title: NEK2 induces drug resistance mainly through activation of efflux drug pumps and is associated with poor prognosis in myeloma and other cancers.
abstract: 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.
authors: Division of Hematology, Oncology, and Blood and Marrow Transplantation, Department of Internal Medicine, University of Iowa, Iowa City, IA 52242, USA.
authors: Wen
authors: W
authors: Zhou
authors: Ye
authors: Y
authors: Yang
authors: Jiliang
authors: J
authors: Xia
authors: He
authors: H
authors: Wang
authors: Mohamed E
authors: ME
authors: Salama
authors: Wei
authors: W
authors: Xiong
authors: Hongwei
authors: H
authors: Xu
authors: Shashirekha
authors: S
authors: Shetty
authors: Tiehua
authors: T
authors: Chen
authors: Zhaoyang
authors: Z
authors: Zeng
authors: Lei
authors: L
authors: Shi
authors: Maurizio
authors: M
authors: Zangari
authors: Rodney
authors: R
authors: Miles
authors: David
authors: D
authors: Bearss
authors: Guido
authors: G
authors: Tricot
authors: Fenghuang
authors: F
authors: Zhan
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000378:metabolism / Q000627:therapeutic use*; D049109:Cell Proliferation; D043171:Chromosomal Instability / Q000235:genetics; D019008:Drug Resistance, Neoplasm / Q000235:genetics*; D005260:Female; D020869:Gene Expression Profiling; D006801:Humans; D008297:Male; D051379:Mice; D009101:Multiple Myeloma / Q000175:diagnosis / Q000188:drug therapy / Q000235:genetics*; D000072379:NIMA-Related Kinases; D011379:Prognosis; D017346:Protein Serine-Threonine Kinases / Q000037:antagonists & inhibitors / Q000235:genetics*; D034622:RNA Interference
chemical_list: D000970:Antineoplastic Agents; C089441:NEK2 protein, human; D000072379:NIMA-Related Kinases; D017346:Protein Serine-Threonine Kinases