title: Cancer cells display profound intra- and interline variation following prolonged exposure to antimitotic drugs.
abstract: Drugs targeting the mitotic spindle are used extensively during chemotherapy, but surprisingly, little is known about how they kill tumor cells. This is largely because many of the population-based approaches are indirect and lead to vague and confusing interpretations. Here, we use a high-throughput automated time-lapse light microscopy approach to systematically analyze over 10,000 single cells from 15 cell lines in response to three different classes of antimitotic drug. We show that the variation in cell behavior is far greater than previously recognized, with cells within any given line exhibiting multiple fates. We present data supporting a model wherein cell fate is dictated by two competing networks, one involving caspase activation, the other protecting cyclin B1 from degradation.
authors.affiliation: Faculty of Life Sciences, University of Manchester, Oxford Road, Manchester M13 9PT, UK.
authors.forename: Karen E
authors.initials: KE
authors.lastname: Gascoigne
authors.forename: Stephen S
authors.initials: SS
authors.lastname: Taylor
mesh_terms: D050256:Antimitotic Agents / Q000494:pharmacology*; D020169:Caspases / Q000378:metabolism; D016923:Cell Death / Q000187:drug effects; D045744:Cell Line, Tumor; D019070:Cell Lineage / Q000187:drug effects*; D043171:Chromosomal Instability / Q000187:drug effects; D002877:Chromosomes, Human / Q000235:genetics; D006801:Humans; D008853:Microscopy; D008938:Mitosis / Q000187:drug effects; D008954:Models, Biological; D009369:Neoplasms / Q000201:enzymology / Q000473:pathology*; D008941:Spindle Apparatus / Q000187:drug effects / Q000378:metabolism; D013997:Time Factors
chemical_list: D050256:Antimitotic Agents; D020169:Caspases