Cytokinesis failure due to derailed integrin traffic induces aneuploidy and oncogenic transformation in vitro and in vivo

G. Högnäs, S. Tuomi, S. Veltel, E. Mattila, A. Murumägi, H. Edgren, O. Kallioniemi, J. Ivaska

    Research output: Contribution to journalArticleScientificpeer-review

    34 Citations (Scopus)


    Aneuploidy is frequently detected in solid tumors but the mechanisms regulating the generation of aneuploidy and their relevance in cancer initiation remain under debate and are incompletely characterized. Spatial and temporal regulation of integrin traffic is critical for cell migration and cytokinesis. Impaired integrin endocytosis, because of the loss of Rab21 small GTPase or mutations in the integrin Β-subunit cytoplasmic tail, induces failure of cytokinesis in vitro. Here, we describe that repeatedly failed cytokinesis, because of impaired traffic, is sufficient to trigger the generation of aneuploid cells, which display characteristics of oncogenic transformation in vitro and are tumorigenic in vivo. Furthermore, in an in vivo mouse xenograft model, non-transformed cells with impaired integrin traffic formed tumors with a long latency. More detailed investigation of these tumors revealed that the tumor cells were aneuploid. Therefore, abnormal integrin traffic was linked with generation of aneuploidy and cell transformation also in vivo. In human prostate and ovarian cancer samples, downregulation of Rab21 correlates with increased malignancy. Loss-of-function experiments demonstrate that long-term depletion of Rab21 is sufficient to induce chromosome number aberrations in normal human epithelial cells. These data are the first to demonstrate that impaired integrin traffic is sufficient to induce conversion of non-transformed cells to tumorigenic cells in vitro and in vivo.

    Original languageEnglish
    Pages (from-to)3597-3606
    Number of pages10
    Issue number31
    Publication statusPublished - 2 Aug 2012
    Publication typeA1 Journal article-refereed


    • aneuploidy
    • cancer
    • cytokinesis
    • integrin traffic

    ASJC Scopus subject areas

    • Molecular Biology
    • Cancer Research
    • Genetics


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