We found a match
Your institution may have access to this item. Find your institution then sign in to continue.
- Title
Inhibition of Aurora-A suppresses epithelial-mesenchymal transition and invasion by downregulating MAPK in nasopharyngeal carcinoma cells.
- Authors
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; Quentin Liu
- Abstract
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.
- Subjects
MITOGEN-activated protein kinases; CANCER cells; CENTROSOMES; PHOSPHORYLATION
- Publication
Carcinogenesis, 2008, Vol 29, Issue 10, p1930
- ISSN
0143-3334
- Publication type
Article
- DOI
10.1093/carcin/bgn176