Aurora kinases are essential for PKC-induced invasion and matrix metalloproteinase-9 expression in MCF-7 breast cancer cells

Oncol Rep. 2015 Aug;34(2):803-10. doi: 10.3892/or.2015.4027. Epub 2015 Jun 4.

Abstract

The Aurora kinase family of serine/threonine kinases are known to be crucial for cell cycle control. Aurora kinases are considered a target of anticancer drugs. However, few studies have assessed the effect of Aurora kinases in breast cancer. In the present study, to determine whether Aurora kinases play a role in oncogenic actions of protein kinase C (PKC), we investigated the effect of Aurora kinases on PKC-induced invasion and MMP-9 expression using breast cancer cells. Treatment of MCF-7 cells with 12-O-tetradecanoylphorbol-13-acetate (TPA) induced the upregulation and phosphorylation of Aurora kinases via the MAPK signaling pathway. Moreover, the inhibition of Aurora kinases by their siRNAs and inhibitors suppressed TPA-induced cell invasion and expression of MMP-9 by inhibiting the activation of NF-κB/AP-1, major transcription factors for MMP-9 expression in MCF-7 cells. These results suggested that Aurora kinases mediate PKC-MAPK signal to NF-κB/AP-1 with increasing MMP-9 expression and invasion of MCF-7 cells. To the best of our knowledge, this is the first study to show that Aurora kinases are key molecules in PKC-induced invasion in breast cancer cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aurora Kinase A / biosynthesis*
  • Aurora Kinase A / genetics
  • Aurora Kinase B / biosynthesis*
  • Aurora Kinase B / genetics
  • Breast Neoplasms / genetics*
  • Breast Neoplasms / pathology
  • Female
  • Gene Expression Regulation, Neoplastic / drug effects
  • Humans
  • MCF-7 Cells
  • Matrix Metalloproteinase 9 / biosynthesis*
  • Matrix Metalloproteinase 9 / genetics
  • Mitogen-Activated Protein Kinase Kinases / genetics
  • NF-kappa B / biosynthesis
  • NF-kappa B / genetics
  • Neoplasm Invasiveness / genetics
  • Protein Kinase C / biosynthesis*
  • Protein Kinase C / genetics
  • Signal Transduction / drug effects
  • Tetradecanoylphorbol Acetate / pharmacology

Substances

  • NF-kappa B
  • Aurora Kinase A
  • Aurora Kinase B
  • Protein Kinase C
  • Mitogen-Activated Protein Kinase Kinases
  • Matrix Metalloproteinase 9
  • Tetradecanoylphorbol Acetate