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Oncogene-like induction of cellular invasion from centrosome amplification

机译：中心体扩增致癌基因样诱导的细胞侵袭

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摘要

Centrosome amplification has long been recognized as a feature of human tumours; however, its role in tumorigenesis remains unclear. Centrosome amplification is poorly tolerated by non-transformed cells and, in the absence of selection, extra centrosomes are spontaneously lost. Thus, the high frequency of centrosome amplification, particularly in more aggressive tumours, raises the possibility that extra centrosomes could, in some contexts, confer advantageous characteristics that promote tumour progression. Using a three-dimensional model system and other approaches to culture human mammary epithelial cells, we find that centrosome amplification triggers cell invasion. This invasive behaviour is similar to that induced by overexpression of the breast cancer oncogene ERBB2 (ref. 4) and indeed enhances invasiveness triggered by ERBB2. Our data indicate that, through increased centrosomal microtubule nudeation, centrosome amplification increases Racl activity, which disrupts normal cell-cell adhesion and promotes invasion. These findings demonstrate that centrosome amplification, a structural alteration of the cytos-keleton, can promote features of malignant transformation.
机译：长久以来，中心体扩增一直被认为是人类肿瘤的特征。然而，其在肿瘤发生中的作用仍不清楚。非转化细胞对中心体扩增的耐受性很差，并且在没有选择的情况下，多余的中心体会自发丢失。因此，中心体扩增的高频率，特别是在更具侵略性的肿瘤中，增加了额外的中心体在某些情况下可以赋予促进肿瘤进展的有利特征的可能性。使用三维模型系统和其他方法来培养人类乳腺上皮细胞，我们发现中心体扩增触发细胞入侵。这种侵袭行为与乳腺癌癌基因ERBB2的过表达诱导的侵袭行为相似（参考文献4），并且确实增强了由ERBB2触发的侵袭性。我们的数据表明，通过增加中心体微管裸露，中心体扩增可增加Racl活性，从而破坏正常细胞与细胞的粘附并促进侵袭。这些发现表明，中心体扩增是细胞-骨架的结构改变，可以促进恶性转化的特征。

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  • 来源
    《Nature》 |2014年第7503期|167-171|共5页
  • 作者

    Susana A. Godinho; Remigio Picone; Mithila Burute; Regina Dagher; Ying Su; Cheuk T. Leung; Kornelia Polyak; Joan S. Brugge; Manuel Thery; David Pellman;

  • 作者单位

    Howard Hughes Medical Institute, Department of Pediatric Oncology, Dana-Farber Cancer Institute and Pediatric Hematology/Oncology, Children's Hospital, Boston, Massachusetts 02115, USA,Department of Cell Biology, Harvard Medical School, Boston, Massachusetts 02115, USA,Barts Cancer Institute, Queen Mary University of London, Charterhouse Square,London EC1M 6BQ, UK;

    Howard Hughes Medical Institute, Department of Pediatric Oncology, Dana-Farber Cancer Institute and Pediatric Hematology/Oncology, Children's Hospital, Boston, Massachusetts 02115, USA,Department of Cell Biology, Harvard Medical School, Boston, Massachusetts 02115, USA;

    Institut de Recherche en Technologie et Science pour le Vivant, UMR5168 CEA/UJF/INRA/CNRS, Grenoble,France,Hopital Saint Louis, Institut Universitaire d'Hematologie, U1160 INSERM/AP-HP/Universite Paris Diderot, Paris 75010, France,CYTOO SA, Grenoble 38054, France;

    Howard Hughes Medical Institute, Department of Pediatric Oncology, Dana-Farber Cancer Institute and Pediatric Hematology/Oncology, Children's Hospital, Boston, Massachusetts 02115, USA,Department of Cell Biology, Harvard Medical School, Boston, Massachusetts 02115, USA;

    Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts 02115, USA;

    Department of Cell Biology, Harvard Medical School, Boston, Massachusetts 02115, USA,Department of Pharmacology, University of Minnesota, Minneapolis, Minnesota 55455, USA;

    Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts 02115, USA;

    Department of Cell Biology, Harvard Medical School, Boston, Massachusetts 02115, USA;

    Institut de Recherche en Technologie et Science pour le Vivant, UMR5168 CEA/UJF/INRA/CNRS, Grenoble,France,Hopital Saint Louis, Institut Universitaire d'Hematologie, U1160 INSERM/AP-HP/Universite Paris Diderot, Paris 75010, France;

    Howard Hughes Medical Institute, Department of Pediatric Oncology, Dana-Farber Cancer Institute and Pediatric Hematology/Oncology, Children's Hospital, Boston, Massachusetts 02115, USA,Department of Cell Biology, Harvard Medical School, Boston, Massachusetts 02115, USA;

  • 收录信息 美国《科学引文索引》(SCI);美国《工程索引》(EI);美国《生物学医学文摘》(MEDLINE);美国《化学文摘》(CA);
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