Tetraploidy in cancer and its possible link to aging

Abstract

Tetraploidy, a condition in which a cell has four homologous sets of chromosomes, is often seen as a natural physiological condition but is also frequently seen in pathophysiological conditions such as cancer. Tetraploidy facilitates chromosomal instability (CIN), which is an elevated level of chromosomal loss and gain that can cause production of a wide variety of aneuploid cells that carry structural and numerical aberrations of chromosomes. The resultant genomic heterogeneity supposedly expedites karyotypic evolution that confers oncogenic potential in spite of the reduced cellular fitness caused by aneuploidy. Recent studies suggest that tetraploidy might also be associated with aging; mice with mutations in an intermediate filament protein have revealed that these tetraploidy‐prone mice exhibit tissue disorders associated with aging. Cellular senescence and its accompanying senescence‐associated secretory phenotype have now emerged as critical factors that link tetraploidy and tetraploidy‐induced CIN with cancer, and possibly with aging. Here, we review recent findings about how tetraploidy is related to cancer and possibly to aging, and discuss underlying mechanisms of the relationship, as well as how we can exploit the properties of cells exhibiting tetraploidy‐induced CIN to control these pathological conditions.

Torsin ATPases influence chromatin interaction of the Torsin regulator LAP1

“…Both binucleation and aneuploidy may contribute to or even drive tumorigenesis (Chow et al, 2012, Levine & Holland, 2018, Tanaka et al, 2018. Because Torsins likely function in a redundant manner, it is highly improbable that Torsin function can be completely abolished by mutations in most tissues.…”

Excessive E2F transcription in single cancer cells precludes transient cell cycle exit after DNA damage

“…. Tetraploidization precedes malignant transformation In various cancer types, and therefore this escape could potentially lead to oncogenic transformation (Davoli, and de Lange, 2011;Tanaka, Goto, et al, 2018). Tetraploidy is associated with the ability of non-transformed cells to form tumors in xenografted mice (Davoli, and de Lange, 2012).…”

Physiology, Development, and Disease Modeling in the Drosophila Excretory System

“…One source that is highly relevant to cancer is whole-genome duplication, or polyploidy. Polyploidy is a driver of elevated genomic instability in numerous contexts, where it promotes unfaithful cell divisions through several mechanisms (Davoli and de Lange 2011;Fox and Duronio 2013;Storchova 2014;Tanaka et al 2018). Further, polyploidy is thought to be the underlying cause of roughly one-third of altered karyotypes in human cancers (Carter et al 2012;Zack et al 2013;Bielski et al 2018).…”