Journal
JOURNAL OF CELL BIOLOGY
Volume 163, Issue 5, Pages 949-961Publisher
ROCKEFELLER UNIV PRESS
DOI: 10.1083/jcb.200307070
Keywords
kinetochore; mitosis; CIN; mitotic spindle; segregation
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Funding
- NIGMS NIH HHS [T32 GM-07377, T32 GM007377] Funding Source: Medline
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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.
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