Targeting the Mitotic Catastrophe Signaling Pathway in Cancer

Figure 2

Mechanisms of mitotic catastrophe. (a) Cells with an abrogated G2 checkpoint will enter mitosis prematurely in the presence of damaged DNA and undergo segregation defects leading to mitotic catastrophe. (b) Cells with defects in mitotic apparatus and/or machinery required for faithful chromosome segregation fail to satisfy the spindle assembly checkpoint (SAC) and undergo prolonged mitotic arrest and mitotic catastrophe. (c) Cytokinesis defects that occur after anaphase will lead to a tetraploid progeny that will undergo mitotic catastrophe in the next M-phase. (d). Following activation of mitotic catastrophe, cells arrested in mitosis have three fates; they will undergo death in mitosis in the presence of cyclin B, or cyclin B levels will gradually fall allowing the cells to undergo slippage and exit mitosis where they subsequently undergo death in G1. Alternatively, cells can undergo senescence following slippage.