Lethality to human cancer cells through massive chromosome loss by inhibition of the mitotic checkpoint

Geert J P L Kops, Daniel R. Foltz, Don W. Cleveland*

*Corresponding author for this work

Research output: Contribution to journalArticle

311 Scopus citations

Abstract

A compromised mitotic checkpoint, the primary mechanism for ensuring that each new cell receives one copy of every chromosome, has been implicated as a contributor to carcinogenesis. However, a checkpoint response is shown here to be essential for cell survival, including that of chromosomally instable colorectal cancer cells. Reducing the levels of the checkpoint proteins BubR1 or Mad2 in human cancer cells or inhibiting BubR1 kinase activity provokes apoptotic cell death within six divisions except when cytokinesis is also inhibited. Thus, suppression of mitotic checkpoint signaling is invariably lethal as the consequence of massive chromosome loss, findings that have implications for inhibiting proliferation of tumor cells.

Original languageEnglish (US)
Pages (from-to)8699-8704
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume101
Issue number23
DOIs
StatePublished - Jun 8 2004

ASJC Scopus subject areas

  • General

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