Journal Article

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

Xiang-Bo Wan, Zi-Jie Long, Min Yan, Jie Xu, Liang-Ping Xia, Li Liu, Yan Zhao, Xue-Fei Huang, Xian-Ren Wang, Xiao-Feng Zhu, Ming-Huang Hong and Quentin Liu

in Carcinogenesis

Volume 29, issue 10, pages 1930-1937
Published in print October 2008 | ISSN: 0143-3334
Published online July 2008 | e-ISSN: 1460-2180 | DOI: http://dx.doi.org/10.1093/carcin/bgn176
Inhibition of Aurora-A suppresses epithelial–mesenchymal transition and invasion by downregulating MAPK in nasopharyngeal carcinoma cells

More Like This

Show all results sharing this subject:

  • Clinical Cytogenetics and Molecular Genetics

GO

Show Summary Details

Preview

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 G2/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 β-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.

Journal Article.  4942 words.  Illustrated.

Subjects: Clinical Cytogenetics and Molecular Genetics

Full text: subscription required

How to subscribe Recommend to my Librarian

Users without a subscription are not able to see the full content. Please, subscribe or login to access all content.