Chromosome instability in colorectal tumor cells is associated with defects in microtubule plus-end attachments caused by a dominant mutation in APC

Rebecca A. Green, Kenneth B. Kaplan

Research output: Contribution to journalArticle

167 Scopus citations

Abstract

The attachment of microtubule plus ends to kinetochores and to the cell cortex is essential for the fidelity of chromosome segregation. Here, we characterize the causes underlying the high rates of chromosome instability (CIN+) observed in colorectal tumor cells. We show that CIN + tumor cells exhibit inefficient microtubule plus-end attachments during mitosis, accompanied by impairment of chromosome alignment in metaphase. The mitotic abnormalities associated with CIN+ tumor cells correlated with status of adenomatous polyposis coli (APC). Importantly, we have shown that a single truncating mutation in APC, similar to mutations found in tumor cells, acts dominantly to interfere with microtubule plus-end attachments and to cause a dramatic increase in mitotic abnormalities. We propose that APC functions to modulate microtubule plus-end attachments during mitosis, and that a single mutant APC allele predisposes cells to increased mitotic abnormalities, which may contribute to tumor progression.

Original languageEnglish (US)
Pages (from-to)949-961
Number of pages13
JournalJournal of Cell Biology
Volume163
Issue number5
DOIs
StatePublished - Dec 8 2003

Keywords

  • CIN
  • Kinetochore
  • Mitosis
  • Mitotic spindle
  • Segregation

ASJC Scopus subject areas

  • Cell Biology

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