The effect of Aurora kinases on cell proliferation, cell cycle regulation and metastasis in renal cell carcinoma

Int J Oncol. 2012 Dec;41(6):2139-49. doi: 10.3892/ijo.2012.1633. Epub 2012 Sep 20.

Abstract

Aurora kinases have been shown to be involved in the regulation of the cell cycle and are related to tumor progression. This suggests the possibility that they can serve as new anticancer targets for tumor treatment. However, the important roles that Aurora kinases and their signaling pathway play in renal cell carcinoma (RCC) are not fully understood and addressed to date. In this study, we aimed to address these questions. We observed that downregulation of Aurora kinases induced by AurA miRNA, AurB miRNA or VX680 could inhibit proliferation and metastasis, induce G2/M phase arrest in clear cell renal cell carcinoma cells and exert antitumor activity in an SN12C xenograft model. We also show that either silencing of Aurora kinases or treating the cells with VX680 could downregulate the expression of cdc25c and cyclin B/cdc2, upregulate the expression of p-cdc2 (Tyr15) via blocking the activity of ERK. All these changes may contribute to inhibition of proliferation, metastasis and G2/M arrest in ccRCC. In summary, we proved that both Aurora kinases A and B are key elements of tumor growth regulation, and inhibition of Aurora kinases may contribute to blocking ccRCC progression. We conclude that Aurora kinases could be potential therapeutic targets in the management of renal cell carcinoma.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Aurora Kinases
  • Carcinoma, Renal Cell / genetics
  • Carcinoma, Renal Cell / metabolism*
  • Carcinoma, Renal Cell / pathology*
  • Cell Cycle Proteins / genetics
  • Cell Cycle Proteins / metabolism
  • Cell Cycle* / drug effects
  • Cell Cycle* / genetics
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Female
  • Gene Expression Regulation, Neoplastic / drug effects
  • Humans
  • Kidney Neoplasms / genetics
  • Kidney Neoplasms / metabolism*
  • Kidney Neoplasms / pathology*
  • Mice
  • Mice, Nude
  • Neoplasm Metastasis / genetics
  • Piperazines / pharmacology
  • Protein-Serine-Threonine Kinases / antagonists & inhibitors
  • Protein-Serine-Threonine Kinases / genetics
  • Protein-Serine-Threonine Kinases / metabolism*
  • RNA Interference
  • Transplantation, Heterologous
  • Tumor Burden / drug effects
  • Tumor Burden / genetics

Substances

  • Cell Cycle Proteins
  • Piperazines
  • VX680
  • Aurora Kinases
  • Protein-Serine-Threonine Kinases