ArticleOncotarget2014
Loss of compensatory pro-survival and anti-apoptotic modulator, IKKε, sensitizes ovarian cancer cells to CHEK1 loss through an increased level of p21.
Article in Oncotarget, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
12 citing papers in PubMed, 14 citations in OpenAlex.
- Clinical outcomes of prexasertib monotherapy in recurrentJournal for immunotherapy of cancer · 2020Trial
- Deciphering Pharmacological Targets of Plumbagin in Cisplatin-resistant Ovarian Cancer Model usingCurrent pharmaceutical design · 2026Article
- Silencing IKBKE inhibits the migration and invasion of glioblastoma by promoting Snail1 degradation.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2022Article
- NF-κB Signaling in Ovarian Cancer.Cancers · 2019Review
- Inhibition of CHK 1 (Checkpoint Kinase 1) Elicits Therapeutic Effects in Pulmonary Arterial Hypertension.Arteriosclerosis, thrombosis, and vascular biology · 2019Article
- BRD4 facilitates DNA damage response and represses CBX5/Heterochromatin protein 1 (HP1).Oncotarget · 2017Article
- Identification of therapeutic targets applicable to clinical strategies in ovarian cancer.BMC cancer · 2016Article
- Characterization of ovarian cancer cell lines as in vivo models for preclinical studies.Gynecologic oncology · 2016Article
- Identification of CHEK1, SLC26A4, c-KIT, TPO and TG as new biomarkers for human follicular thyroid carcinoma.Oncotarget · 2016Article
- Identifying module biomarkers from gastric cancer by differential correlation network.OncoTargets and therapy · 2016Article
- Identification of new biomarkers for human papillary thyroid carcinoma employing NanoString analysis.Oncotarget · 2015Article
- Topotecan synergizes with CHEK1 (CHK1) inhibitor to induce apoptosis in ovarian cancer cells.BMC cancer · 2015Article
Corrections and comments
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Authors and funding
5 authors at 3 institutions in 1 country.
Funding
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 demonstrated that the depletion of p21 rendered OC cells more resistant to cell death induced by co-inhibition of IKKε and CHEK1. In conclusion, we revealed a novel interplay between IKKε, CHEK1 and p21 signaling in survival of OC. Our study provides a rationale for the clinical development of specific IKKε inhibitor and for usage of IKKε as an exploratory marker for resistance to CHEK1 inhibitors in the clinic. The interplay provides one potential explanation as to why very few clinical responses were achieved in patients treated with single-agent CHEK1 inhibitors.
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Registered trials
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