Formation of extra centrosomal structures is dependent on β-catenin
Formation of extra centrosomal structures is dependent on β-catenin
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DOI：
10.1242/jcs.064782
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发表时间：
2010-09-15
影响因子：
4
通讯作者：
Barth, Angela I. M.
中科院分区：
文献类型：
--
作者：
Bahmanyar, Shirin;Guiney, Evan L.;Barth, Angela I. M.
β-连环蛋白在细胞-细胞粘附和基因转录调节中具有重要作用。稳定β-连环蛋白的突变在癌症中很常见，但目前尚不清楚这些突变如何促进癌症进展。β-连环蛋白也是参与中心体分离的中心体组分。在正常细胞中，中心体使间期微管和双极有丝分裂纺锤体成核，但它们在人类癌症中的组织和功能异常。在这里，我们表明，稳定的突变体β-连环蛋白的表达，它模仿癌症中发现的突变，导致额外的非微管成核结构，包含一个子集的中心体蛋白，包括γ-微管蛋白和中心蛋白，但不polo样激酶4（Plk 4），SAS-6或pericentrin。β-连环蛋白的转录失活形式也引起中心体蛋白的异常结构。缺失突变型β-连环蛋白等位基因的HCT 116人结肠癌细胞系具有减少的具有异常中心体结构和S期停滞的扩增的中心体的细胞数量。RNAi介导的β-连环蛋白从中心体的耗竭抑制了中心体的S期阻滞扩增。这些结果表明，β-连环蛋白是中心体扩增所必需的，β-连环蛋白的突变可能有助于在癌症中观察到的异常中心体的形成。
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.