ArticleThe EMBO journal2023
IκB kinase-α coordinates BRD4 and JAK/STAT signaling to subvert DNA damage-based anticancer therapy.
Article in The EMBO journal, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed, 24 citations in OpenAlex.
- Hsa-miR-5585-3p regulates the NLRP3 activation and the expression of cytokines through CHUK in a cellular model of diabetic kidney disease.BMC endocrine disorders · 2026Article
- The roles of IKKα in normal physiology and cancer.Cell communication and signaling : CCS · 2026Review
- Bromodomain-containing protein 4 in inflammatory diseases: molecular mechanisms and therapeutic potential.Journal of inflammation (London, England) · 2026Review
- The Molecular and Functional Landscape of Resistance to FOLFIRI Chemotherapy in Metastatic Colorectal Cancer.Cancer discovery · 2026Article
- Glucose deprivation drives LIF-dependent lung cancer.Nature metabolism · 2026Article
- Article
- Tight junction-high and CDH17-positive cell population is the source of colorectal cancer liver metastases.Nature communications · 2026Article
- Immune signaling as a determinant of cellular identity and tissue function.Frontiers in immunology · 2026Review
- Targeting the FOSL1/IKKα positive feedback loop attenuates glioblastoma malignancyTheranostics · 2026Article
- HIV-1 latency reversing agents converge on phosphoregulation of nuclear protein complexes.bioRxiv : the preprint server for biology · 2025Article
- Double trouble: cytosolic and nuclear IKKα in cancer.Open biology · 2025Review
- BRD4 interacting genes as prognostic biomarkers in hepatocellular carcinoma for optimized treatment strategies.Scientific reports · 2025Article
- A combinatorial screening protocol for identifying novel and highly potent dual-target inhibitor of BRD4 and STAT3 for kidney cancer therapy.Frontiers in pharmacology · 2025Article
- Acetylation-Mediated Epigenetic Consequences for Biological Control and Cancer.Results and problems in cell differentiation · 2025Review
- Key Role of STAT3 in Osteoarthritis: From Pathogenic Mechanisms to Targeted Therapy.International journal of nanomedicine · 2025Review
- Defective kinase activity of IKKα leads to combined immunodeficiency and disruption of immune tolerance in humans.Nature communications · 2024Article
- NFκB signalling in colorectal cancer: Examining the central dogma of IKKα and IKKβ signalling.Heliyon · 2024Review
- NF-κB in biology and targeted therapy: new insights and translational implications.Signal transduction and targeted therapy · 2024Review
- Targeting the JAK-STAT pathway in colorectal cancer: mechanisms, clinical implications, and therapeutic potential.Frontiers in cell and developmental biology · 2024Review
- IκB kinase-α coordinates BRD4 and JAK/STAT signaling to subvert DNA damage-based anticancer therapy.The EMBO journal · 2023Article
Corrections and comments
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Authors and funding
23 authors at 8 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Activation of the IκB kinase (IKK) complex has recurrently been linked to colorectal cancer (CRC) initiation and progression. However, identification of downstream effectors other than NF-κB has remained elusive. Here, analysis of IKK-dependent substrates in CRC cells after UV treatment revealed that phosphorylation of BRD4 by IKK-α is required for its chromatin-binding at target genes upon DNA damage. Moreover, IKK-α induces the NF-κB-dependent transcription of the cytokine LIF, leading to STAT3 activation, association with BRD4 and recruitment to specific target genes. IKK-α abrogation results in defective BRD4 and STAT3 functions and consequently irreparable DNA damage and apoptotic cell death upon different stimuli. Simultaneous inhibition of BRAF-dependent IKK-α activity, BRD4, and the JAK/STAT pathway enhanced the therapeutic potential of 5-fluorouracil combined with irinotecan in CRC cells and is curative in a chemotherapy-resistant xenograft model. Finally, coordinated expression of LIF and IKK-α is a poor prognosis marker for CRC patients. Our data uncover a functional link between IKK-α, BRD4, and JAK/STAT signaling with clinical relevance.
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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.