Combined AURKA and H3K9 Methyltransferase Targeting Inhibits Cell Growth By Inducing Mitotic Catastrophe.

ABSTRACT: The current integrative pathobiologic hypothesis states that pancreatic cancer (PDAC) develops and progresses in response to an interaction between known oncogenes and downstream epigenomic regulators. Congruently, this study tests a new combinatorial therapy based on the inhibition of the Aurora kinase A (AURKA) oncogene and one of its targets, the H3K9 methylation-based epigenetic pathway. This therapeutic combination is effective at inhibiting the in vitro growth of PDAC cells both, in monolayer culture systems, and in three-dimensional spheroids and organoids. The combination also reduces the growth of PDAC xenografts in vivo Mechanistically, it was found that inhibiting methyltransferases of the H3K9 pathway in cells, which are arrested in G₂-M after targeting

SUBMITTER: Mathison A 

PROVIDER: S-EPMC5705946 | biostudies-literature | 2017 Aug

REPOSITORIES: biostudies-literature