NEK2 Induces Drug Resistance Mainly through Activation of Efflux Drug Pumps and Is Associated with Poor Prognosis in Myeloma and Other Cancers

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• 作者：Wen Zhou¹ ; ³ ; ⁶ ; Ye Yang¹ ; ³ ; ⁶ ; Jiliang Xia¹ ; ³ ; ⁶ ; He Wang¹ ; ³ ; ⁶ ; Mohamed E. Salama² ; Wei Xiong³ ; Hongwei Xu¹ ; ³ ; Shashirekha Shetty⁴ ; Tiehua Chen³ ; Zhaoyang Zeng³ ; Lei Shi³ ; Maurizio Zangari³ ; Rodney Miles² ; David Bearss⁵ ; Guido Tricot¹ ; ^{guido-tricot@uiowa.edu} ; Fenghuang Zhan¹ ; ³ ; ^{fenghuang-zhan@uiowa.edu}
• 刊名：Cancer Cell
• 出版年：2013
• 出版时间：14 January, 2013
• 年：2013
• 卷：23
• 期：1
• 页码：48-62
• 全文大小：3349 K

文摘

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Summary

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.