title: Molecular pathways: regulation and targeting of kinetochore-microtubule attachment in cancer.
abstract: 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.
authors.affiliation: Department of Biochemistry and Molecular Biology, Colorado State University, Fort Collins, Colorado.
authors.forename: Jacob A
authors.initials: JA
authors.lastname: Herman
authors.affiliation: Human Biology Division, Fred Hutchinson Cancer Research Center, Seattle, Washington. Molecular and Cellular Biology Program, University of Washington, Seattle, Washington.
authors.forename: Chad M
authors.initials: CM
authors.lastname: Toledo
authors.affiliation: Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, Washington.
authors.forename: James M
authors.initials: JM
authors.lastname: Olson
authors.affiliation: Department of Biochemistry and Molecular Biology, Colorado State University, Fort Collins, Colorado. Jennifer.Deluca@ColoState.edu paddison@fhcrc.org.
authors.forename: Jennifer G
authors.initials: JG
authors.lastname: DeLuca
authors.affiliation: Human Biology Division, Fred Hutchinson Cancer Research Center, Seattle, Washington. Molecular and Cellular Biology Program, University of Washington, Seattle, Washington. Jennifer.Deluca@ColoState.edu paddison@fhcrc.org.
authors.forename: Patrick J
authors.initials: PJ
authors.lastname: Paddison
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology* / Q000627:therapeutic use; D006801:Humans; D018386:Kinetochores / Q000187:drug effects / Q000502:physiology*; D059566:M Phase Cell Cycle Checkpoints; D008870:Microtubules / Q000187:drug effects; D058990:Molecular Targeted Therapy; D009369:Neoplasms / Q000188:drug therapy* / Q000473:pathology; D011485:Protein Binding
chemical_list: D000970:Antineoplastic Agents
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