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

Wen Zhou, Ye Yang, Jiliang Xia, He Wang, Mohamed E. Salama, Wei Xiong, Hongwei Xu, Shashirekha Shetty, Tiehua Chen, Zhaoyang Zeng, Lei Shi, Maurizio Zangari, Rodney Miles, David Bearss, Guido Tricot, Fenghuang Zhan

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125 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)48-62
Number of pages15
JournalCancer cell
Volume23
Issue number1
DOIs
StatePublished - Jan 14 2013

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ASJC Scopus subject areas

  • Oncology
  • Cell Biology
  • Cancer Research

Cite this

Zhou, W., Yang, Y., Xia, J., Wang, H., Salama, M. E., Xiong, W., Xu, H., Shetty, S., Chen, T., Zeng, Z., Shi, L., Zangari, M., Miles, R., Bearss, D., Tricot, G., & Zhan, F. (2013). NEK2 Induces Drug Resistance Mainly through Activation of Efflux Drug Pumps and Is Associated with Poor Prognosis in Myeloma and Other Cancers. Cancer cell, 23(1), 48-62. https://doi.org/10.1016/j.ccr.2012.12.001