Mitosis and apoptosis: how is the balance set?

ABSTRACT

Anti-mitotic agents are used extensively during cancer chemotherapy. These agents target microtubules and thus block mitotic progression by activating the spindle assembly checkpoint. Following a prolonged mitotic arrest, cells either die in mitosis via apoptosis, or exit mitosis without dividing and survive, a process known as slippage. What dictates the balance between these two fates is unclear, but recent advances highlight the importance of the pro-survival Bcl2 family, with Mcl1 degradation emerging as a key determinant of mitotic cell fate. Here we review these advances, with a view towards identifying how the balance between apoptosis and slippage can be tipped in favour of death. This in turn may open up new opportunities to sensitize cancer cells to anti-mitotic agents.