Formation of extra centrosomal structures is dependent on β-catenin

Abstract

β-Catenin has important roles in cell–cell adhesion and in the regulation of gene transcription. Mutations that stabilize β-catenin are common in cancer, but it remains unclear how these mutations contribute to cancer progression. β-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 β-catenin, which mimics mutations found in cancer, results in extra non-microtubule nucleating structures that contain a subset of centrosome proteins including γ-tubulin and centrin, but not polo-like kinase 4 (Plk4), SAS-6 or pericentrin. A transcriptionally inactive form of β-catenin also gives rise to abnormal structures of centrosome proteins. HCT116 human colon cancer cell lines, from which the mutant β-catenin allele has been deleted, have reduced numbers of cells with abnormal centrosome structures and S-phase-arrested, amplified centrosomes. RNAi-mediated depletion of β-catenin from centrosomes inhibits S-phase-arrested amplification of centrosomes. These results indicate that β-catenin is required for centrosome amplification, and mutations in β-catenin might contribute to the formation of abnormal centrosomes observed in cancers.