Chromosomal instability (CIN) is widely considered a hallmark of cancer, but its 
precise roles in cancer stem cells (CSC) and malignant progression remain 
uncertain. BMI1 is a member of the Polycomb group of chromatin-modifier proteins 
that is essential for stem cell self-renewal. In human cancers, BMI1 
overexpression drives stem-like properties associated with induction of 
epithelial-mesenchymal transition (EMT) that promotes invasion, metastasis, and 
poor prognosis. Here, we report that BMI1 mediates its diverse effects through 
upregulation of the mitotic kinase Aurora A, which is encoded by the AURKA gene. 
Two mechanisms were found to be responsible for BMI1-induced AURKA expression. 
First, BMI1 activated the Akt pathway, thereby upregulating AURKA expression 
through activation of the β-catenin/TCF4 transcription factor complex. Second, 
BMI1 repressed miRNA let-7i through a Polycomb complex-dependent mechanism, 
thereby relieving AURKA expression from let-7i suppression. AURKA upregulation 
by BMI1 exerts several effects, including centrosomal amplification and 
aneuploidy, antiapoptosis, and cell-cycle progression through p53 degradation 
and EMT through stabilization of Snail. Inhibiting Aurora A kinase activity 
attenuated BMI1-induced tumor growth in vivo. In clinical specimens of head and 
neck cancer, we found that coamplification of BMI1 and AURKA correlated with 
poorer prognosis. Together, our results link CSCs, EMT, and CIN through the 
BMI1-AURKA axis and suggest therapeutic use from inhibiting Aurora A in head and 
neck cancers, which overexpress BMI1.