Dynamics of cytokinesis failure in individual tumorigenic cells

Normal progression through the cell division cycle is essential for a healthy organism. Disruptions in the cell cycle can lead to a range of abnormalities, including the formation of a genomically unstable tumor. Failure of cytokinesis, the final step of the cell cycle, can result in multinucleation, which alone is sufficient to promote tumorigenesis. Multinucleation has also been associated with a resistance to chemotherapeutic drugs and an increased probability of mutations. Here, we investigated the spatiotemporal dynamics with which a mother cell fails to undergo cytokinesis and gives rise to multinucleated progeny. We compared two well-established cell lines: MCF10A human mammary epithelial cells, and SCp2 mouse mammary epithelial cells. On a cell-by-cell basis, we compared the morphologies and behaviors of mother cells that successfully completed cytokinesis with those that became multinucleated. These comparisons revealed several different parameters that influence cytokinesis, including the stiffness of the extracellular matrix, the migratory behaviors of the cells, and the relative lengths of different stages of the cell cycle. These findings influence our conception of how genomic instabilities that drive cancer progression are initiated.