Phosphorylation and Activation of Cell Division Cycle Associated 8 by Aurora Kinase B Plays a Significant Role in Human Lung Carcinogenesis
| Autor: | Yusuke Nakamura, Tatsuya Kato, Satoshi Hayama, Tomoo Ito, Satoshi Kondo, Eiju Tsuchiya, Masaki Miyamoto, Yataro Daigo, Takumi Yamabuki, Daizaburo Hirata |
|---|---|
| Rok vydání: | 2007 |
| Předmět: |
Cancer Research
Small interfering RNA Cell Membrane Permeability Lung Neoplasms Cell division Molecular Sequence Data Cell Cycle Proteins Cell Growth Processes Protein Serine-Threonine Kinases Biology medicine.disease_cause Aurora kinase Aurora Kinases Cell Line Tumor medicine Aurora Kinase B Humans Amino Acid Sequence Phosphorylation RNA Small Interfering Lung cancer Cell cycle Prognosis medicine.disease Oncology Immunology Cancer cell Cancer research Peptides Carcinogenesis E2F1 Transcription Factor |
| Zdroj: | Cancer Research. 67:4113-4122 |
| ISSN: | 1538-7445 0008-5472 |
| Popis: | Through genome-wide gene expression analysis of lung carcinomas, we detected in the great majority of lung cancer samples cotransactivation of cell division cycle associated 8 (CDCA8) and aurora kinase B (AURKB), which were considered to be components of the vertebrate chromosomal passenger complex. Immunohistochemical analysis of lung cancer tissue microarrays showed that overexpression of CDCA8 and AURKB was significantly associated with poor prognosis of lung cancer patients. AURKB directly phosphorylated CDCA8 at Ser154, Ser219, Ser275, and Thr278 and seemed to stabilize CDCA8 protein in cancer cells. Suppression of CDCA8 expression with small interfering RNA against CDCA8 significantly suppressed the growth of lung cancer cells. In addition, functional inhibition of interaction between CDCA8 and AURKB by a cell-permeable peptide corresponding to 20-amino acid sequence of a part of CDCA8 (11R-CDCA8261–280), which included two phosphorylation sites by AURKB, significantly reduced phosphorylation of CDCA8 and resulted in growth suppression of lung cancer cells. Our data imply that selective suppression of the CDCA8-AURKB pathway could be a promising therapeutic strategy for treatment of lung cancer patients. [Cancer Res 2007;67(9):4113–22] |
| Databáze: | OpenAIRE |
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