Loss of compensatory pro-survival and anti-apoptotic modulator, IKKε, sensitizes ovarian cancer cells to CHEK1 loss through an increased level of p21.

ABSTRACT: Ovarian cancer (OC) is extremely heterogeneous, implying that therapeutic strategies should be specifically designed based on molecular characteristics of an individual's tumor. Previously, we showed that IKKε promotes invasion and metastasis in a subset of OCs. Here, we identified CHEK1 as an IKKε-dependent lethal gene from shRNA kinome library screen. In subsequent pharmacological intervention studies, the co-inhibition of IKKε and CHEK1 was more effective in killing OC cells than single treatment. At the molecular level, co-inhibition dramatically decreased pro-survival proteins, but increased proteins involved in DNA damage and apoptosis. IKKε-knockdown increased p21 levels, while overexpression of wild-type IKKε, but not a kinase dead IKKε mutant decreased p21 levels. We further demon

SUBMITTER: Kim MK 

PROVIDER: S-EPMC4350339 | biostudies-literature | 2014 Dec

REPOSITORIES: biostudies-literature