title: Formation of extra centrosomal structures is dependent on beta-catenin.
abstract: beta-Catenin has important roles in cell-cell adhesion and in the regulation of gene transcription. Mutations that stabilize beta-catenin are common in cancer, but it remains unclear how these mutations contribute to cancer progression. beta-Catenin is also a centrosomal component involved in centrosome separation. Centrosomes nucleate interphase microtubules and the bipolar mitotic spindle in normal cells, but their organization and function in human cancers are abnormal. Here, we show that expression of stabilized mutant beta-catenin, which mimics mutations found in cancer, results in extra non-microtubule nucleating structures that contain a subset of centrosome proteins including gamma-tubulin and centrin, but not polo-like kinase 4 (Plk4), SAS-6 or pericentrin. A transcriptionally inactive form of beta-catenin also gives rise to abnormal structures of centrosome proteins. HCT116 human colon cancer cell lines, from which the mutant beta-catenin allele has been deleted, have reduced numbers of cells with abnormal centrosome structures and S-phase-arrested, amplified centrosomes. RNAi-mediated depletion of beta-catenin from centrosomes inhibits S-phase-arrested amplification of centrosomes. These results indicate that beta-catenin is required for centrosome amplification, and mutations in beta-catenin might contribute to the formation of abnormal centrosomes observed in cancers.
authors.affiliation: Department of Biology, Stanford University, Stanford, CA 94305, USA.
authors.forename: Shirin
authors.initials: S
authors.lastname: Bahmanyar
authors.forename: Evan L
authors.initials: EL
authors.lastname: Guiney
authors.forename: Emily M
authors.initials: EM
authors.lastname: Hatch
authors.forename: W James
authors.initials: WJ
authors.lastname: Nelson
authors.forename: Angela I M
authors.initials: AI
authors.lastname: Barth
mesh_terms: D000818:Animals; D002453:Cell Cycle; D045744:Cell Line, Tumor; D018385:Centrosome / Q000737:chemistry* / Q000378:metabolism*; D004285:Dogs; D006801:Humans; D009369:Neoplasms / Q000235:genetics / Q000378:metabolism*; D014404:Tubulin / Q000235:genetics / Q000378:metabolism; D051176:beta Catenin / Q000235:genetics / Q000378:metabolism*
chemical_list: D014404:Tubulin; D051176:beta Catenin