Overexpression of PAD4 suppresses drug resistance of NSCLC cell lines to gefitinib through inhibiting Elk1-mediated epithelial-mesenchymal transition

  • Authors:
    • Qiong Duan
    • Cui Pang
    • Ning Chang
    • Ju Zhang
    • Wenchao Liu
  • View Affiliations

  • Published online on: April 28, 2016     https://doi.org/10.3892/or.2016.4780
  • Pages: 551-558
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Abstract

It is reported that epithelial-to-mesenchymal transition (EMT) could induce resistance in tumor cells, and knockdown of peptidylarginine deiminase IV (PAD4) induces the activity of EMT. However, the role of PAD4 in gefitinib‑acquired resistance in non-small cell lung cancer (NSCLC) remains unclear. In this study, we aimed to investigate the role of PAD4 in the resistance of NSCLC to gefitinib. The cells resistant to gefitinib were established in accordance with the literature, and were derived from NSCLC cell lines HCC827 and H1650. Real-time quantitative PCR and western blot results showed that PAD4 was obviously downregulated in the cells resistant to gefitinib. Overexpression of PAD4 distinctly inhibited gefitinib resistance, whereas PAD4 downregulation had the opposite effect. Further data indicated that PAD4 upregulation could restrain EMT activity via controlling the expression of ETS-domain containing protein (Elk1). Conversely, inhibition of PAD4 showed the reverse function compared with PAD4 upregulation. Above all, our study showed that overexpression of PAD4 constrains the activity of EMT via suppressing Elk1 expression, and inhibits resistance of NSCLC to gefitinib.
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July-2016
Volume 36 Issue 1

Print ISSN: 1021-335X
Online ISSN:1791-2431

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Spandidos Publications style
Duan Q, Pang C, Chang N, Zhang J and Liu W: Overexpression of PAD4 suppresses drug resistance of NSCLC cell lines to gefitinib through inhibiting Elk1-mediated epithelial-mesenchymal transition. Oncol Rep 36: 551-558, 2016
APA
Duan, Q., Pang, C., Chang, N., Zhang, J., & Liu, W. (2016). Overexpression of PAD4 suppresses drug resistance of NSCLC cell lines to gefitinib through inhibiting Elk1-mediated epithelial-mesenchymal transition. Oncology Reports, 36, 551-558. https://doi.org/10.3892/or.2016.4780
MLA
Duan, Q., Pang, C., Chang, N., Zhang, J., Liu, W."Overexpression of PAD4 suppresses drug resistance of NSCLC cell lines to gefitinib through inhibiting Elk1-mediated epithelial-mesenchymal transition". Oncology Reports 36.1 (2016): 551-558.
Chicago
Duan, Q., Pang, C., Chang, N., Zhang, J., Liu, W."Overexpression of PAD4 suppresses drug resistance of NSCLC cell lines to gefitinib through inhibiting Elk1-mediated epithelial-mesenchymal transition". Oncology Reports 36, no. 1 (2016): 551-558. https://doi.org/10.3892/or.2016.4780