New Insights into p53 Signaling and Cancer Cell Response to DNA Damage: Implications for Cancer Therapy

Figure 8

Formation and fate of multinucleated/polyploid giant cancer cells. Ionizing radiation triggers the development of giant cells within cultures of cancer cells lacking wild-type (WT) p53 function. In addition, although p53 wild-type cancer cells respond to ionizing radiation by undergoing SIPS, a small proportion of cells “escape” from the SIPS response and give rise to multinucleated/polyploid giants. While some giant cells may die through apoptosis, others may undergo complex genome-reduction processes (e.g., depolyploidization; neosis), ultimately giving rise to rapidly-proliferating progeny. The mitotic kinase Aurora B plays an important role in regulating the survival of giant cells. Recent evidence suggests that ATM may prevent the propagation of giant cells and their descendants by activating protein phosphatase 1 (PP1) and inhibiting Aurora B kinase activity (for details, consult [34]).