IL-7/IL-7 receptor axis stimulates prostate cancer cell invasion and migration via AKT/NF-κB pathway

Int Immunopharmacol. 2016 Nov:40:203-210. doi: 10.1016/j.intimp.2016.08.017. Epub 2016 Sep 7.

Abstract

IL-7, acting via IL-7 receptor (IL-7R), plays an important role in tumor progression. Elevated IL-7 expression has been reported to be observed in prostate cancer tissues and closely associated with poor prognosis. However, the biological functions of IL-7 and its receptor in prostate cancer cell invasiveness remain unclear. In our study, we found that the expressions of IL-7 and IL-7R were both upregulated in prostate cancer cells. IL-7 dose-dependently promoted the invasion and migration of prostate cancer cells, whereas knockdown of IL-7R attenuated the effect of IL-7. Further, IL-7/IL-7R axis induced the activation of AKT and NF-κB, whereas blocking of AKT suppressed IL-7-mediated NF-κB activity. Moreover, IL-7/IL-7R axis increased MMP-3 and MMP-7 expression of prostate cancer cells, whereas inhibition of NF-κB as well as MMPs activity suppressed IL-7-mediated cell invasion and migration. Together, these data identify IL-7/IL-7R axis to be involved in prostate cancer cell invasion and migration, probably via activating AKT/NF-κB pathway and upregulating MMP-3 and MMP-7 expression. Therefore, blocking IL-7/IL-7R axis may provide a potential therapeutic strategy to treat prostate cancer.

Keywords: AKT; IL-7; IL-7R; Invasion; NF-κB; Prostate cancer.

MeSH terms

  • Cell Line
  • Cell Line, Tumor
  • Cell Movement / physiology
  • Humans
  • Interleukin-7 / metabolism*
  • Male
  • Matrix Metalloproteinase 3 / metabolism
  • Matrix Metalloproteinase 7 / metabolism
  • NF-kappa B / metabolism*
  • Neoplasm Invasiveness
  • Prostatic Neoplasms / metabolism*
  • Prostatic Neoplasms / pathology
  • Proto-Oncogene Proteins c-akt / metabolism*
  • Receptors, Interleukin-7 / metabolism*
  • Signal Transduction

Substances

  • Interleukin-7
  • NF-kappa B
  • Receptors, Interleukin-7
  • Proto-Oncogene Proteins c-akt
  • MMP3 protein, human
  • Matrix Metalloproteinase 3
  • MMP7 protein, human
  • Matrix Metalloproteinase 7