Differential sensitivity of Glioma stem cells to Aurora kinase A inhibitors: Implications for stem cell mitosis and centrosome dynamics

• Glioma stem cells (GSC) exhibit aberrant cell division and increased polyploidy
• Centrosome maturation is abnormal and GSC survival is Aurora A dependent
• Inhibition of Aurora A increases spindle defects, polyploidy and senescence in GSC
• GSC are selectively sensitive to Aurora A and Plk1 inhibitors
• This is a novel strategy to target GSC and improve outcomes in glioblastoma

Glioma stem-cell-like cells are considered to be responsible for treatment resistance and tumour recurrence following chemo-radiation in glioblastoma patients, but specific targets by which to kill the cancer stem cell population remain elusive. A characteristic feature of stem cells is their ability to undergo both symmetric and asymmetric cell divisions. In this study we have analysed specific features of glioma stem cell mitosis. We found that glioma stem cells appear to be highly prone to undergo aberrant cell division and polyploidization. Moreover, we discovered a pronounced change in the dynamic of mitotic centrosome maturation in these cells. Accordingly, glioma stem cell survival appeared to be strongly dependent on Aurora A activity. Unlike differentiated cells, glioma stem cells responded to moderate Aurora A inhibition with spindle defects, polyploidization and a dramatic increase in cellular senescence, and were selectively sensitive to Aurora A and Plk1 inhibitor treatment. Our study proposes inhibition of centrosomal kinases as a novel strategy to selectively target glioma stem cells.