ArticleOncogene2013
Non-canonical Notch signaling activates IL-6/JAK/STAT signaling in breast tumor cells and is controlled by p53 and IKKα/IKKβ.
Article in Oncogene, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 96 papers.
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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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Who cites it
96 citing papers in PubMed, 139 citations in OpenAlex.
- Trial
- The JAK/STAT pathway: a pivotal therapeutic target in disease and advances in natural product modulation.Molecular diversity · 2026Review
- Notch receptors in breast cancer: context-dependent roles and therapeutic targeting.Cell communication and signaling : CCS · 2026Review
- Disrupting Notch signalling by a small molecule inhibiting dihydroorotate dehydrogenase activity.Scientific reports · 2026Article
- The Blockade of Delta-Like Ligand 1 Inhibits Atherosclerotic Lesion Formation and Attenuates Plaque Vulnerability.Journal of atherosclerosis and thrombosis · 2026Article
- Ligand-Specific Notch Signaling in Atherosclerosis: Implications for Inflammation and Plaque Stability.Journal of atherosclerosis and thrombosis · 2026Article
- Emphysema Shapes a Pro-Inflammatory Immune Microenvironment in Pulmonary Adenocarcinoma: A Pilot Immune Transcriptomic Profiling Study.International journal of molecular sciences · 2026Article
- JAK2 and NOTCH2 in gastric cancer - NOTCH2 is an independent prognosticator of poor patient outcome.Virchows Archiv : an international journal of pathology · 2026Article
- Venom-Derived Proteins fromInternational journal of molecular sciences · 2026Article
- The Multifaceted Roles of STAT6: Implications for Precision Immunotherapeutics.ImmunoTargets and therapy · 2026Review
- Current research of the Notch pathway in hepatocellular carcinoma.European journal of medical research · 2025Review
- Significance of Notch Signaling in Salivary Gland Development and Diseases.Journal of clinical medicine · 2025Review
- Recent advances and future perspectives in small molecule JAK2 inhibitors.Future medicinal chemistry · 2025Review
- Canonical and noncanonical NOTCH signaling in the nongenetic resistance of cancer: distinct and concerted control.Frontiers of medicine · 2025Review
- Notch signaling in cancer: metabolic reprogramming and therapeutic implications.Frontiers in immunology · 2025Review
- Targeting the Key Signaling Pathways in Breast Cancer: From Molecular Mechanism to Therapeutic Interventions.Recent patents on anti-cancer drug discovery · 2025Review
- Notch signaling pathway in cancer: from mechanistic insights to targeted therapies.Signal transduction and targeted therapy · 2024Review
- NRN1 interacts with Notch to increase oncogenic STAT3 signaling in melanoma.Cell communication and signaling : CCS · 2024Article
- Identification of a Notch transcriptomic signature for breast cancer.Breast cancer research : BCR · 2024Article
- Ginsenoside Rh2 regulates triple-negative breast cancer proliferation and apoptosis via the IL-6/JAK2/STAT3 pathway.Frontiers in pharmacology · 2024Article
36 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
16 authors at 7 institutions in 4 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Notch signaling is frequently hyperactivated in breast cancer, but how the enhanced signaling contributes to the tumor process is less well understood. In this report, we identify the proinflammatory cytokine interleukin-6 (IL-6) as a novel Notch target in breast tumor cells. Enhanced Notch signaling upregulated IL-6 expression, leading to activation of autocrine and paracrine Janus kinase/signal transducers and activators of transcription signaling. IL-6 upregulation was mediated by non-canonical Notch signaling, as it could be effectuated by a cytoplasmically localized Notch intracellular domain and was independent of the DNA-binding protein CSL. Instead, Notch-mediated IL-6 upregulation was controlled by two proteins in the nuclear factor (NF)-κB signaling cascade, IKKα and IKKβ (inhibitor of nuclear factor kappa-B kinase subunit alpha and beta, respectively), as well as by p53. Activation of IL-6 by Notch required IKKα/IKKβ function, but interestingly, did not engage canonical NF-κB signaling, in contrast to IL-6 activation by inflammatory agents such as lipopolysaccharide. With regard to p53 status, IL-6 expression was upregulated by Notch when p53 was mutated or lost, and restoring wild-type p53 into p53-mutated or -deficient cells abrogated the IL-6 upregulation. Furthermore, Notch-induced transcriptomes from p53 wild-type and -mutated breast tumor cell lines differed extensively, and for a subset of genes upregulated by Notch in a p53-mutant cell line, this upregulation was reduced by wild-type p53. In conclusion, we identify IL-6 as a novel non-canonical Notch target gene, and reveal roles for p53 and IKKα/IKKβ in non-canonical Notch signaling in breast cancer and in the generation of cell context-dependent diversity in the Notch signaling output.
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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.