Aneuploidy is a hallmark of human cancers originating from abnormal mitoses. Many aneuploid cancer cells also have greater-than-diploid DNA content, suggesting that polyploidy is a common precursor to aneuploidy during tumor progression. Polyploid cells can originate from cell fusion, endoreplication, and cytokinesis failure. Recently we found that cell cannibalism by entosis, a form of cell engulfment involving live cells, also leads to polyploidy, as internalized cells disrupt cytokinesis of their engulfing cell hosts. By this mechanism, cannibalistic cell behavior could promote tumor progression by leading to aneuploidy. Here, we discuss cell cannibalism in cancer and other mechanisms that result in the formation of polyploid cancer cells.
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"That these percentages were higher than indicated by the FACS data is probably explained by the large size of some polyploid cells causing them to evade FACS analysis. Polyploidy can be caused by several mechanisms: abnormal mitosis, endoreduplication, cell fusion and entosis (Krajcovic and Overholtzer, 2012). Given that cell appearance does not distinguish between the products of cell fusion and mitotic failure, and that entosis has been observed mainly under non-adherent growth conditions (Overholtzer et al., 2007), we tested the extent to which these different processes were responsible for baseline and post-treatment levels of polyploidy amongst GSCs. "
[Show abstract][Hide abstract]ABSTRACT: Glioma stem-cell-like cells are considered to be responsible for treatment resistance and tumour recurrence following chemo-radiation in glioblastoma patients, but specific targets by which to kill the cancer stem cell population remain elusive. A characteristic feature of stem cells is their ability to undergo both symmetric and asymmetric cell division. In this study we have analysed specific features of glioma stem cell mitosis. We found that glioma stem cells appear to be highly prone to undergo aberrant cell division and polyploidization. Moreover, we discovered a pronounced change in the dynamic of mitotic centrosome maturation in these cells. Accordingly, glioma stem cell survival appeared to be strongly dependent on Aurora A activity. Unlike differentiated cells, glioma stem cells responded to moderate Aurora A inhibition with spindle defects, polyploidization and a dramatic increase in cellular senescence, and were selectively sensitive to Aurora A and Plk1 inhibitor treatment. Our study proposes inhibition of centrosomal kinases as a novel strategy to selectively target glioma stem cells.
Full-text · Article · Jul 2014 · Stem Cell Research
[Show abstract][Hide abstract]ABSTRACT: It is well known that the karyotype of animal cells cultured in vitro tends to become aneuploid as the culture ages. Aneuploidy can cause genetic instability, alter the biological properties of cells, and affect their application in genetic studies and cell engineering. Understanding the causes and mechanisms of aneuploidy is primary to control its occurrence in cultured cells, and is also helpful to understand the mechanisms of tumorigenesis because aneuploidy is a hallmark of tumor cells. This review underscores the potential role of reactive oxygen species (ROS) toxicity in spontaneous aneuploidy of cultured cells. The underlying mechanisms and possible sources of ROS are also discussed.
[Show abstract][Hide abstract]ABSTRACT: Polyploidy, or whole-genome duplication (WGD), is a recurrent mutation both in cell lineages and over evolutionary time. By globally changing the relationship between gene copy number and other cellular entities, it can induce dramatic changes at the cellular and phenotypic level. Perhaps surprisingly, then, the insights that these events can bring to understanding other cellular features are not as well appreciated as they could be. In this review, we draw on examples of polyploidy from animals, plants and yeast to explore how investigations of polyploid cells have improved our understanding of the cell cycle, biological network complexity, metabolic phenotypes and tumor biology. We argue that the study of polyploidy across organisms, cell types, and time scales serves not only as a window into basic cell biology, but also as a basis for a predictive biology with applications ranging from crop improvement to treating cancer.
Full-text · Article · Mar 2013 · Seminars in Cell and Developmental Biology