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84 Aurora kinase B as a potential therapeutic target of cervical cancer
  1. Paul Chan
  1. The Chinese University of Hong Kong, Shatin, New Territories,, China


Introduction/Background Human papillomavirus (HPV) contributes to approximately 5% of human cancers and 7.5% of cancer deaths in women. Recent reports showed that members of the Aurora (Aur) kinase family are involved in HPV-mediated carcinogenesis. This study delineated the molecular interactions between HPV-E6 and AurB, and investigated its consequences on key oncogenic pathways.

Methodology In vitro and cell-based assays were used to examine the physical association between E6 and AurB, and its consequences on key oncogenic pathways, including the effect on human telomerase reverse transcriptase (hTERT) protein level and its telomerase activity. The effect of Aurora kinase inhibitors on the hallmarks of cancer phenotype was studied using 3-dimensional (3D) in vitro and in vivo models.

Results 1. AurB interacted directly with E6 at a region located upstream of the C-terminal E6-PBM.

2. AurB-E6 complex formation resulted in the reduction of AurB kinase activity, whereas an elevation of hTERT protein level and its telomerase activity were observed.

3. AurB inhibition by treatment with specific compounds led to a decrease in the telomerase activity, cell proliferation, and tumor formation.

Conclusion The Aur-E6 complex formation could be essential in maintaining the cancer phenotype of HPV-mediated cancers. Therefore, inhibiting Aur-E6 complex formation could be a specific therapeutic target of cervical cancer and other HPV-associated cancers. Further studies in this direction to explore novel therapeutic targets are worthwhile.

Disclosures This project was funded by Research Grants Council, Hong Kong SAR Government

(RGF Ref No. 14162117).

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