ArticleProceedings of the National Academy of Sciences of the United States of America2013
IKK epsilon kinase is crucial for viral G protein-coupled receptor tumorigenesis.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 24 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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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
24 citing papers in PubMed, 38 citations in OpenAlex.
- Evaluation of human papillomavirus as a risk factor in prostate cancer pathogenesis.Discover oncology · 2025Review
- KSHV hijacks the antiviral kinase IKKε to initiate lytic replication.PLoS pathogens · 2025Article
- Anoikis resistance--protagonists of breast cancer cells survive and metastasize after ECM detachment.Cell communication and signaling : CCS · 2023Review
- The Targeting of Nuclear Factor Kappa B by Drugs Adopted for the Prevention and Treatment of Preeclampsia.International journal of molecular sciences · 2022Review
- I-κB kinase-ε deficiency improves doxorubicin-induced dilated cardiomyopathy by inhibiting the NF-κB pathway.Frontiers in physiology · 2022Article
- PKD3 promotes metastasis and growth of oral squamous cell carcinoma through positive feedback regulation with PD-L1 and activation of ERK-STAT1/3-EMT signalling.International journal of oral science · 2021Article
- I-Oxidative medicine and cellular longevity · 2021Article
- IKKε phosphorylates kindlin-2 to induce invadopodia formation and promote colorectal cancer metastasis.Theranostics · 2020Article
- Advances in IKBKE as a potential target for cancer therapy.Cancer medicine · 2020Review
- A positive feedback between IDO1 metabolite and COL12A1 via MAPK pathway to promote gastric cancer metastasis.Journal of experimental & clinical cancer research : CR · 2019Article
- IΚΚε cooperates with either MEK or non-canonical NF-kB driving growth of triple-negative breast cancer cells in different contexts.BMC cancer · 2018Article
- The regulatory role of protein phosphorylation in human gammaherpesvirus associated cancers.Virologica Sinica · 2017Review
- Hyper activation of β-catenin signalling induced by IKKε inhibition thwarts colorectal cancer cell proliferation.Cell proliferation · 2017Article
- Detection of IKKε by immunohistochemistry in primary breast cancer: association with EGFR expression and absence of lymph node metastasis.BMC cancer · 2017Article
- Roles of IκB kinase ε in the innate immune defense and beyond.Virologica Sinica · 2016Review
- Hijacking GPCRs by viral pathogens and tumor.Biochemical pharmacology · 2016Review
- IKBKE Is a Substrate of EGFR and a Therapeutic Target in Non-Small Cell Lung Cancer with Activating Mutations of EGFR.Cancer research · 2016Article
- Recent advances on viral manipulation of NF-κB signaling pathway.Current opinion in virology · 2015Review
- Diallyl disulfide inhibits TNFα induced CCL2 release through MAPK/ERK and NF-Kappa-B signaling.Cytokine · 2015Article
- An Internally Translated MAVS Variant Exposes Its Amino-terminal TRAF-Binding Motifs to Deregulate Interferon Induction.PLoS pathogens · 2015Article
Corrections and comments
- Erratum issuedGutkind, Julio S [corrected to Gutkind, J Silvio]
Authors and funding
11 authors at 3 institutions in 2 countries.
Funding
Abstract
G protein-coupled receptors (GPCRs) are seven-transmembrane proteins that transmit diverse extracellular signals across a membrane. Herpesvirus genomes encode multiple GPCRs implicated in viral pathogenesis. Kaposi sarcoma-associated herpesvirus GPCR (kGPCR) activates proliferative pathways and, when expressed in endothelium in mice, sufficiently induces angiogenic tumor resembling human Kaposi's sarcoma. IKKε, an IκB kinase (IKK)-related kinase, is implicated in inflammation-driven tumorigenesis. We report here that IKKε is critically required for kGPCR tumorigenesis and links kGPCR to NF-κB activation. Using kGPCR-induced tumor models, we found that IKKε expression was drastically up-regulated in Kaposi sarcoma-like lesions and that loss of IKKε abolished tumor formation. Moreover, kGPCR interacted with and activated IKKε. Activated IKKε promoted NF-κB subunit RelA (also known as p65) phosphorylation, which correlated with NF-κB activation and inflammatory cytokine expression. The robust expression of IKKε and phosphorylated RelA was observed in human Kaposi sarcoma. Finally, a kinase-defective mutant of IKKε effectively abrogated NF-κB activation and tumorigenesis induced by kGPCR. Collectively, our findings uncover a critical IKKε in promoting NF-κB activation and tumorigenesis induced by a viral GPCR.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.