Inhibition of Aurora-A suppresses epithelial-mesenchymal transition and invasion by downregulating MAPK in nasopharyngeal carcinoma cells

Carcinogenesis. 2008 Oct;29(10):1930-7. doi: 10.1093/carcin/bgn176. Epub 2008 Jul 30.


Mitotic serine/threonine kinase Aurora-A (Aur-A) plays a critical role in regulating centrosome segregation and spindle assemble. Aur-A overexpression causes excessive centrosome duplication and abnormal spindle structure, leading to tumor malignant progression. Here, we investigated Aur-A expression in nasopharyngeal carcinoma (NPC) and the association between Aur-A and NPC invasiveness. We showed that overexpression of Aur-A in tumor tissues was correlated with cranial bone invasion and clinical stage in NPC patients. Suppression of Aur-A by either selective Aurora inhibitory VX-680 or small-interfering RNA caused G(2)/M arrest and apoptotic cell death in NPC CNE-2 cells. Significantly, inhibition of Aur-A suppressed CNE-2 cell invasion and restored membrane expression of epithelial markers, E-cadherin and beta-catenin, suggesting a reversed epithelial-mesenchymal transition process in cancer cells. In addition, we found that Aur-A-regulated epithelial-mesenchymal transition and invasion were mediated by mitogen-activated protein kinase (MAPK) phosphorylation. Moreover, suppression of MAP kinase by small-interfering RNA or its upstream MEK1/2-selective inhibitor U0126 abrogated cell invasion enhanced by Aur-A overexpression. On the other hand, forced overexpression of constitutively active form of MEK1/2, MEK2DD, in CNE-2 cancer cells rescued cell invasive ability suppressed by VX-680-imposed Aur-A inhibition. Our results indicated that Aur-A acted through a downstream MAP kinase pathway to promote epithelial-mesenchymal transition and invasiveness in nasopharyngeal tumorigenesis. Small chemical inhibitor VX-680 may offer as a promising molecular targeting agent in human NPC.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Apoptosis / drug effects
  • Aurora Kinases
  • Butadienes / pharmacology
  • Cadherins / analysis
  • Cell Line, Tumor
  • Down-Regulation
  • Epithelium / pathology*
  • Humans
  • MAP Kinase Signaling System
  • Mesoderm / pathology*
  • Middle Aged
  • Mitogen-Activated Protein Kinases / antagonists & inhibitors*
  • Mitogen-Activated Protein Kinases / metabolism
  • Nasopharyngeal Neoplasms / enzymology
  • Nasopharyngeal Neoplasms / etiology
  • Nasopharyngeal Neoplasms / pathology*
  • Neoplasm Invasiveness
  • Neoplasm Staging
  • Nitriles / pharmacology
  • Phosphorylation
  • Piperazines / pharmacology
  • Protein Serine-Threonine Kinases / antagonists & inhibitors
  • Protein Serine-Threonine Kinases / physiology*
  • RNA, Small Interfering / pharmacology
  • beta Catenin / analysis


  • Butadienes
  • Cadherins
  • Nitriles
  • Piperazines
  • RNA, Small Interfering
  • U 0126
  • beta Catenin
  • tozasertib
  • Aurora Kinases
  • Protein Serine-Threonine Kinases
  • Mitogen-Activated Protein Kinases