Different cell fates after mitotic slippage: From aneuploidy to polyploidy.
The molecular mechanism responsible for cell fate after mitotic slippage remains unclear. We investigated the different postmitotic effects of aneuploidy versus polyploidy using chemical inhibitors of centromere-associated protein-E (CENP-E) and kinesin family member 11 (KIF11, also known as Eg5). Aneuploidy caused substantial proteotoxic stress and DNA damage accompanied by p53-mediated postmitotic apoptosis, whereas polyploidy did not induce these antiproliferative effects.
Oncology Drug Discovery Unit, Pharmaceutical Research Division, Takeda Pharmaceutical Company Limited , Fujisawa, Japan.
Akihiro
A
Ohashi
Aneuploidy; DNA damage response; mechanisms of oncogenesis and tumor progression; mitotic inhibitor; mitotic slippage; mode of action of anticancer agents; novel therapeutic agents; novel therapeutic targets; oncogenes and tumor suppressor genes; p53; polyploidy; proteotoxic stress; spindle assembly checkpoint; unfolded protein response