Transient endoreplication down-regulates the kinesin-14 HSET and contributes to genomic instability.

ABSTRACT: Polyploid cancer cells exhibit chromosomal instability (CIN), which is associated with tumorigenesis and therapy resistance. The mechanisms that induce polyploidy and how these mechanisms contribute to CIN are not fully understood. Here we evaluate CIN in human cells that become polyploid through an experimentally induced endoreplication cycle. When these induced endoreplicating cells (iECs) returned to mitosis, it resulted in aneuploidy in daughter cells. This aneuploidy resulted from multipolar divisions, chromosome missegregation, and failure in cytokinesis. The iECs went through several rounds of division, ultimately spawning proliferative cells of reduced ploidy. iECs have reduced levels of the kinesin-14 HSET, which likely accounts for the multipolar divisions, and overexpression of

SUBMITTER: Chen S 

PROVIDER: S-EPMC5042578 | biostudies-literature | 2016 Oct

REPOSITORIES: biostudies-literature