Near-tetraploid cancer cells show chromosome instability triggered by replication stress and exhibit enhanced invasiveness.

ABSTRACT: A considerable proportion of tumors exhibit aneuploid karyotypes, likely resulting from the progressive loss of chromosomes after whole-genome duplication. Here, by using isogenic diploid and near-tetraploid (4N) single-cell-derived clones from the same parental cell lines, we aimed at exploring how polyploidization affects cellular functions and how tetraploidy generates chromosome instability. Gene expression profiling in 4N clones revealed a significant enrichment of transcripts involved in cell cycle and DNA replication. Increased levels of replication stress in 4N cells resulted in DNA damage, impaired proliferation caused by a cell cycle delay during S phase, and higher sensitivity to S phase checkpoint inhibitors. In fact, increased levels of replication stress were also observed in

SUBMITTER: Wangsa D 

PROVIDER: S-EPMC5998968 | biostudies-literature | 2018 Jul

REPOSITORIES: biostudies-literature