ArticleMolecular cell2012
IKKα activation of NOTCH links tumorigenesis via FOXA2 suppression.
Article in Molecular cell, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 53 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
53 citing papers in PubMed, 90 citations in OpenAlex.
- The roles of IKKα in normal physiology and cancer.Cell communication and signaling : CCS · 2026Review
- Post translational modification regulation of transcription factors governing pancreatic β-cell identity and functional mass.Frontiers in endocrinology · 2025Review
- Defective kinase activity of IKKα leads to combined immunodeficiency and disruption of immune tolerance in humans.Nature communications · 2024Article
- Conserved Molecular Players Involved in Human Nose Morphogenesis Underlie Evolution of the Exaggerated Snout Phenotype in Cichlids.Genome biology and evolution · 2023Article
- Construction and validation of a prognostic model based on stage-associated signature genes of head and neck squamous cell carcinoma: a bioinformatics study.Annals of translational medicine · 2022Article
- FoXA2 promotes esophageal squamous cell carcinoma progression by ZEB2 activation.World journal of surgical oncology · 2021Article
- Inactivation of FOXA2 by Respiratory Bacterial Pathogens and Dysregulation of Pulmonary Mucus Homeostasis.Frontiers in immunology · 2020Review
- Article
- Transcriptional Regulation Factors of the Human Mitochondrial Aspartate/Glutamate Carrier Gene, Isoform 2 (International journal of molecular sciences · 2019Article
- Hepatocyte Nuclear Factor 3β Plays a Suppressive Role in Colorectal Cancer Progression.Frontiers in oncology · 2019Article
- Notch-Mediated Tumor-Stroma-Inflammation Networks Promote Invasive Properties and CXCL8 Expression in Triple-Negative Breast Cancer.Frontiers in immunology · 2019Article
- Cancer driver mutations in endometriosis: Variations on the major theme of fibrogenesis.Reproductive medicine and biology · 2018Review
- Article
- Cancer Cells Exploit Notch Signaling to Redefine a Supportive Cytokine Milieu.Frontiers in immunology · 2018Review
- The NEDD8 E3 ligase DCNL5 is phosphorylated by IKK alpha during Toll-like receptor activation.PloS one · 2018Article
- SUMOylation and phosphorylation cross-talk in hepatocellular carcinoma.Translational gastroenterology and hepatology · 2018Review
- Crosstalk between the Notch signaling pathway and non-coding RNAs in gastrointestinal cancers.Oncology letters · 2018Article
- The role of Notch signaling in gastric carcinoma: molecular pathogenesis and novel therapeutic targets.Oncotarget · 2017Review
- In vitro generation of mature midbrain-type dopamine neurons by adjusting exogenous Nurr1 and Foxa2 expressions to their physiologic patterns.Experimental & molecular medicine · 2017Article
- Forkhead box A2 regulates biliary heterogeneity and senescence during cholestatic liver injury in mice‡.Hepatology (Baltimore, Md.) · 2017Article
Corrections and comments
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Authors and funding
19 authors at 6 institutions in 2 countries.
Funding
Abstract
Proinflammatory cytokine TNFα plays critical roles in promoting malignant cell proliferation, angiogenesis, and tumor metastasis in many cancers. However, the mechanism of TNFα-mediated tumor development remains unclear. Here, we show that IKKα, an important downstream kinase of TNFα, interacts with and phosphorylates FOXA2 at S107/S111, thereby suppressing FOXA2 transactivation activity and leading to decreased NUMB expression, and further activates the downstream NOTCH pathway and promotes cell proliferation and tumorigenesis. Moreover, we found that levels of IKKα, pFOXA2 (S107/111), and activated NOTCH1 were significantly higher in hepatocellular carcinoma tumors than in normal liver tissues and that pFOXA2 (S107/111) expression was positively correlated with IKKα and activated NOTCH1 expression in tumor tissues. Therefore, dysregulation of NUMB-mediated suppression of NOTCH1 by TNFα/IKKα-associated FOXA2 inhibition likely contributes to inflammation-mediated cancer pathogenesis. Here, we report a TNFα/IKKα/FOXA2/NUMB/NOTCH1 pathway that is critical for inflammation-mediated tumorigenesis and may provide a target for clinical intervention in human cancer.
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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.