Reduced SKP1 Expression Induces Chromosome Instability through Aberrant Cyclin E1 Protein Turnover.

ABSTRACT: Chromosome instability (CIN), or progressive changes in chromosome numbers, is an enabling feature of many cancers; however, the mechanisms giving rise to CIN remain poorly understood. To expand our mechanistic understanding of the molecular determinants of CIN in humans, we employed a cross-species approach to identify 164 human candidates to screen. Using quantitative imaging microscopy (QuantIM), we show that silencing 148 genes resulted in significant changes in CIN-associated phenotypes in two distinct cellular contexts. Ten genes were prioritized for validation based on cancer patient datasets revealing frequent gene copy number losses and associations with worse patient outcomes. QuantIM determined silencing of each gene-induced CIN, identifying novel roles for each as chromosome st

SUBMITTER: Thompson LL 

PROVIDER: S-EPMC7139525 | biostudies-literature | 2020 Feb

REPOSITORIES: biostudies-literature