Kinetochores are large protein structures assembled on centromeric DNA during mitosis that bind to microtubules of the mitotic spindle to orchestrate and power chromosome movements. Deregulation of kinetochore-microtubule (KT-MT) attachments has been implicated in driving chromosome instability and cancer evolution; however, the nature and source of KT-MT attachment defects in cancer cells remain largely unknown. Here, we highlight recent findings suggesting that oncogene-driven changes in kinetochore regulation occur in glioblastoma multiforme (GBM) and possibly other cancers exhibiting chromosome instability, giving rise to novel therapeutic opportunities. In particular, we consider the GLE2p-binding sequence domains of BubR1 and the newly discovered BuGZ, two kinetochore-associated proteins, as candidate therapeutic targets for GBM.
©2014 American Association for Cancer Research.