Aneuploid colon cancer cells have a robust spindle checkpoint

Anthony Tighe, Victoria L. Johnson, Mark Albertella, Stephen S. Taylor

    Research output: Contribution to journalArticlepeer-review


    Colon cancer cells frequently display minisatellite instability (MIN) or chromosome instability (CIN). While MIN is caused by mismatch repair defects, the lesions responsible for CIN are unknown. The observation that CIN cells fail to undergo mitotic arrest following spindle damage suggested that mutations in spindle checkpoint genes may account for CIN. However, here we show that CIN cells do undergo mitotic arrest in response to spindle damage. Although the maximum mitotic index achieved by CIN lines is diminished relative to MIN lines, CIN cells clearly have a robust spindle checkpoint. Consistently, mutations in spindle checkpoint genes are rare in human tumours. In contrast, the adenomatous polyposis coli (APC) gene is frequently mutated in CIN cells. Significantly, we show here that expression of an APC mutant in MIN cells reduces the mitotic index following spindle damage to a level observed in CIN cells, suggesting that APC dysfunction may contribute to CIN.
    Original languageEnglish
    Pages (from-to)609-614
    Number of pages5
    JournalEMBO reports
    Issue number7
    Publication statusPublished - 2001


    Dive into the research topics of 'Aneuploid colon cancer cells have a robust spindle checkpoint'. Together they form a unique fingerprint.

    Cite this