XB-ART-3913Mol Interv May 1, 2003; 3 (3): 127-30.
Aurora-A overexpression leads to override of the microtubule-kinetochore attachment checkpoint.
The amplification of AURORA-A is frequently observed in specific epithelial cell malignancies. The overexpression of aurora-A, a Ser-Thr kinase known to localize to centrosomes during mitosis, appears to imbue cancerous cells with resistance to spindle-checkpoint-targeting drugs such as paclitaxel (Taxol). Indeed, a recent publication by Anand et al. indicates that overexpression of AURORA-A may interfere with spindle-microtubule attachment and disrupt the regulation of the spindle checkpoint by allowing cells with abnormal chromosomal separation to enter anaphase. Thus, the design of new drugs that specifically target aurora-A rather than other checkpoint proteins might alleviate the resistance to Taxol-like clinical therapeutics observed in some tumors.
PubMed ID: 14993419
Article link: Mol Interv
Genes referenced: aurka tbx2