title: 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.
authors.affiliation: Faculty of Life Sciences, University of Manchester, Manchester M13 9PT, UK.
authors.forename: Caroline H
authors.initials: CH
authors.lastname: Topham
authors.forename: Stephen S
authors.initials: SS
authors.lastname: Taylor
mesh_terms: D050256:Antimitotic Agents / Q000494:pharmacology* / Q000627:therapeutic use; D000970:Antineoplastic Agents / Q000494:pharmacology* / Q000627:therapeutic use; D017209:Apoptosis / Q000187:drug effects* / Q000502:physiology*; D051017:Apoptosis Regulatory Proteins / Q000378:metabolism; D051023:BH3 Interacting Domain Death Agonist Protein / Q000378:metabolism; D000072224:Bcl-2-Like Protein 11; D006801:Humans; D008565:Membrane Proteins / Q000378:metabolism; D008870:Microtubules / Q000187:drug effects / Q000378:metabolism; D008938:Mitosis / Q000187:drug effects* / Q000502:physiology*; D008954:Models, Biological; D064549:Myeloid Cell Leukemia Sequence 1 Protein / Q000378:metabolism; D009369:Neoplasms / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology*; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D051020:bcl-X Protein / Q000378:metabolism
chemical_list: D050256:Antimitotic Agents; D000970:Antineoplastic Agents; D051017:Apoptosis Regulatory Proteins; C000606775:BCL2L11 protein, human; D051023:BH3 Interacting Domain Death Agonist Protein; D000072224:Bcl-2-Like Protein 11; D008565:Membrane Proteins; D064549:Myeloid Cell Leukemia Sequence 1 Protein; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D051020:bcl-X Protein