Inhibition of KPNA4 attenuates prostate cancer metastasis

J. Yang, C. Lu, J. Wei, Y. Guo, W. Liu, L. Luo, G. Fisch, Xin Li

Research output: Contribution to journalArticle

Abstract

Prostate cancer (PCa) is a common cancer in men. Although current treatments effectively palliate symptoms and prolong life, the metastatic PCa remains incurable. It is important to find biomarkers and targets to improve metastatic PCa diagnosis and treatment. Here we report a novel correlation between karyopherin α4 (KPNA4) and PCa pathological stages. KPNA4 mediates the cytoplasm-to-nucleus translocation of transcription factors, including nuclear factor kappa B, although its role in PCa was largely unknown. We find that knockdown of KPNA4 reduces cell migration in multiple PCa cell lines, suggesting a role of KPNA4 in PCa progression. Indeed, stable knockdown of KPNA4 significantly reduces PCa invasion and distant metastasis in mouse models. Functionally, KPNA4 alters tumor microenvironment in terms of macrophage polarization and osteoclastogenesis by modulating tumor necrosis factor (TNF)-α and-β. Further, KPNA4 is proved as a direct target of miR-708, a tumor-suppressive microRNA. We disclose the role of miR-708-KPNA4-TNF axes in PCa metastasis and KPNA4's potential as a novel biomarker for PCa metastasis.

Original languageEnglish (US)
Pages (from-to)2868-2878
Number of pages11
JournalOncogene
Volume36
Issue number20
DOIs
StatePublished - May 18 2017

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Prostatic Neoplasms
Neoplasm Metastasis
Tumor Necrosis Factor-alpha
Biomarkers
Karyopherins
Tumor Microenvironment
NF-kappa B
MicroRNAs
Osteogenesis
Cell Movement
Neoplasms
Cytoplasm
Transcription Factors
Macrophages
Cell Line
Therapeutics

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Cancer Research

Cite this

Yang, J., Lu, C., Wei, J., Guo, Y., Liu, W., Luo, L., ... Li, X. (2017). Inhibition of KPNA4 attenuates prostate cancer metastasis. Oncogene, 36(20), 2868-2878. https://doi.org/10.1038/onc.2016.440

Inhibition of KPNA4 attenuates prostate cancer metastasis. / Yang, J.; Lu, C.; Wei, J.; Guo, Y.; Liu, W.; Luo, L.; Fisch, G.; Li, Xin.

In: Oncogene, Vol. 36, No. 20, 18.05.2017, p. 2868-2878.

Research output: Contribution to journalArticle

Yang, J, Lu, C, Wei, J, Guo, Y, Liu, W, Luo, L, Fisch, G & Li, X 2017, 'Inhibition of KPNA4 attenuates prostate cancer metastasis', Oncogene, vol. 36, no. 20, pp. 2868-2878. https://doi.org/10.1038/onc.2016.440
Yang J, Lu C, Wei J, Guo Y, Liu W, Luo L et al. Inhibition of KPNA4 attenuates prostate cancer metastasis. Oncogene. 2017 May 18;36(20):2868-2878. https://doi.org/10.1038/onc.2016.440
Yang, J. ; Lu, C. ; Wei, J. ; Guo, Y. ; Liu, W. ; Luo, L. ; Fisch, G. ; Li, Xin. / Inhibition of KPNA4 attenuates prostate cancer metastasis. In: Oncogene. 2017 ; Vol. 36, No. 20. pp. 2868-2878.
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