Persistently Activated Stat3 Maintains Constitutive NF-κB Activity in Tumors
Open accessAbstract
NF-kappaB (RelA) is constitutively active in many cancers, where it upregulates antiapoptotic and other oncogenic genes. While proinflammatory stimulus-induced NF-kappaB activation involves IKK-dependent nuclear translocation, mechanisms for maintaining constitutive NF-kappaB activity in tumors have not been elucidated. We show here that maintenance of NF-kappaB activity in tumors requires Stat3, which is also frequently constitutively activated in cancer. Stat3 prolongs NF-kappaB nuclear retention through acetyltransferase p300-mediated RelA acetylation, thereby interfering with NF-kappaB nuclear export. Stat3-mediated maintenance of NF-kappaB activity occurs in both cancer cells and tumor-associated hematopoietic cells. Both murine and human cancers display highly acetylated RelA, which is associated with Stat3 activity. This Stat3/NF-kappaB interaction is thus central to both the transformed and nontransformed elements in tumors.
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Some studies suggest cooperation between STAT3 and NF-κB, while others show antagonism.
“Some suggest cooperation between them, while others show antagonism2, 16–21.”
From Synergistic gene expression during the acute phase response is characterized by transcription factor assisted loading (2017) · cites this paper as [20]
The crosstalk between STAT3 and NF-κB is an active field of research with studies showing contradictory outcomes of concomitant activation of the two TFs.
“The crosstalk between STAT3 and NF-κB is an active field of research with studies showing contradictory outcomes of concomitant activation of the two TFs.”
From Synergistic gene expression during the acute phase response is characterized by transcription factor assisted loading (2017) · cites this paper as [20]
STAT3 prolongs NF-κB nuclear retention through acetyltransferase p300-mediated RelA acetylation, thereby interfering with NF-κB nuclear export in both cancer cells and tumor-associated hematopoietic cells.
“For example, STAT3 prolongs NF-κB nuclear retention through acetyltransferase p300-mediated RelA acetylation, thereby interfering with NF-κB nuclear export in both cancer cells and tumor-associated hematopoietic cells (277).”
From IL-6 in inflammation, autoimmunity and cancer (2021) · cites this paper as [277]
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- Authors
- Lee, H., Herrmann, A., Deng, J.-H., Kujawski, M., Niu, G., Li, Z., Forman, S., Jove, R., Pardoll, D. M., & Yu, H.
- Affiliations
- City Of Hope National Medical Center (US)
- Moffitt Cancer Center (US)
- Johns Hopkins University (US)
- Corresponding author
- Pardoll, Drew M.
- Yu, Hua
- Venue
- Cancer Cell
- Publisher
- Elsevier BV
- Published
- 2009-04
- Volume
- 15
- Issue
- 4
- Pages
- 283-293
- ISSN
- 1535-6108 (ISSN-L)
- PMC
- PMC2777654
- OpenAlex
- W2059287377
- Cited by
- 683
- References
- 4
- Citations by year
- 2026: 23 · 2025: 37 · 2024: 36 · 2023: 26 · 2022: 40 · 2021: 41 · 2020: 29 · 2019: 45 · 2018: 28 · 2017: 42 · 2016: 28 · 2015: 43 · 2014: 62 · 2013: 61 · 2012: 43
- FWCI
- 15.89
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Cancer Cell (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- Hope Center for Neurological Disorders
- National Institutes of Health
- National Cancer Institute (P50CA107399, R01CA115674, R01CA122976, R01CA115815)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › NF-κB Signaling Pathways
- Health Sciences › Medicine › Oncology › Cytokine Signaling Pathways and Interactions
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Signaling Pathways in Disease
- Keywords
- STAT3, NF-κB, RelA, P300, malignant transformation, oncogenic signaling
- MeSH terms
- p300-CBP-Associated Factor, Acetylation, Animals, Fluorescent Antibody Technique, Hematopoietic System, Histone Deacetylases, Humans, Male, Melanoma, Phosphorylation, Prostatic Neoplasms, Tumor Cells, Cultured, Immunoblotting, Signal Transduction, Transcriptional Activation, NF-kappa B, Mice, Knockout, Integrases, Active Transport, Cell Nucleus, Electrophoretic Mobility Shift Assay, Immunoprecipitation, STAT3 Transcription Factor, p300-CBP Transcription Factors, Mice
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