Chromosome 20q amplification regulates in vitro response to Kinesin-5 inhibitor

We identified gene expression signatures predicting responsiveness to a Kinesin-5 (kinesin spindle protein, KIF11) inhibitor (Kinesin-5i) in cultured colon tumor cell lines. Genes predicting resistance to Kinesin-5i were enriched for those from chromosome 20q, a region of frequent amplification in a number of tumor types. siRNAs targeting genes in this chromosomal region identified AURKA, TPX2 and MYBL2 as genes whose disruption enhances response to Kinesin-5i. Taken together, our results show functional interaction between these genes, and suggest that overexpression of AURKA, TPX2 and MYBL2 is functionally involved in resistance to Kinesin-5i. Furthermore, our results suggest that patients whose tumors overexpress AURKA due to amplifications of 20q will be more likely to resist treatment with Kinesin-5 inhibitor, and that inactivation of AURKA may sensitize these patients to treatment. Keywords: Cell line comparison A series of colon cancer cell lines was analyzed for gene expression signatures. These gene expression signatures were then correlated with in vitro responsiveness of each cell line to a KSP inhibitor (Kinesin-5i). Transcripts whose expression was correlated with response (>0.5 or <-0.5) were identified as reporters of cellular response to this inhibitor. Reporters were further tested by RNAi for functional role in response to this inhibitor.