Near-tetraploid cells exhibit chromosome instability triggered by replication stress and enhanced invasive capabilities [expression]
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ABSTRACT: A considerable proportion of tumors exhibit aneuploid karyotypes, likely resulting from the loss of chromosomes following whole genome duplication. Here, by using isogenic diploid and near-tetraploid clones derived from the same parental cell line, we aimed at exploring how polyploidization affects cellular functions and how tetraploidy generates chromosome instability. Gene expression profiling in near-tetraploid clones revealed a significant enrichment of genes involved in replication stress. This increased level of replication stress resulted in DNA damage, greater sensitivity to S-phase checkpoint inhibitors, and impaired proliferation caused by a cell cycle delay during S-phase. Additionally, replication stress promoted higher levels of intercellular heterogeneity and ongoing genomic instability, which we observed in the form of abnormal anaphases and prometaphase events. Finally, our data unveiled that near-tetraploid cells displayed increased migratory and invasive capacities, both in vitro and in primary colorectal tumors, thus providing physiological advantages to the cancer cell.
ORGANISM(S): Homo sapiens
PROVIDER: GSE81394 | GEO | 2017/05/10
SECONDARY ACCESSION(S): PRJNA321436
REPOSITORIES: GEO
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