Signal transduction of inflammatory cytokines and tumor development
Open accessAbstract
It has been estimated that >20% of all malignancies are initiated or exacerbated by inflammation. Until recently, the molecular basis of this process has not been clarified. However, recent studies have uncovered the molecular mechanism of intracellular signaling pathways of inflammatory cytokines such as tumor necrosis factor (TNF)-alpha, interferon (IFN)-gamma and interleukin (IL)-6. Three major transcription factors including NF-kappaB, STAT1 and STAT3 have been shown to play major roles in transmitting inflammatory cytokine signals to the nucleus. One function of NF-kappaB and STAT3 in tumor cells is the promotion of cell growth and cell survival through the induction of target genes, whose products promote cell division and inhibit apoptosis. In addition, NF-kappaB and STAT1 are important transcription factors that induce inflammatory mediators from inflammatory cells, especially macrophages, while STAT3 often antagonizes this process. STAT1 is generally believed to be an anti-oncogene because it promotes apoptosis through p53, but it could promote inflammation-mediated tumor development by enhancing tissue injury, remodeling, fibrosis and inflammation. Hence, the inhibition of NF-kappaB and STATs offers a strategy for treatment of a variety of malignancies and can convert inflammation-induced tumor growth into inflammation-induced tumor regression.
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NF-κB is maintained latent in the cytoplasm complexed to IκB; upon activation, IκB-α is phosphorylated by IκB kinases, leading to proteasome-dependent degradation of IκB and rapid translocation of NF-κB into the nucleus, where p65:p50 binding to DNA results in transcription of proinflammatory genes such as cytokines and iNOS/COX-2.
“NF-κB is maintained as a latent form in the cytoplasm of cells where it is complexed to IκB inhibitor protein. Seven members of the IκB family of proteins have been identified and includes IκB-α. Upon activation of NF-κB, IκB-α is phosphorylated by IκB kinases (IKK) leading to proteasome-dependent degradation of IκB, which allows a rapid translocation of NF-κB into the nucleus where it binds to”
From Antioxidant and Anti-Inflammatory Activities of Essential Oils: A Short Review (2010) · cites this paper as [127]
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Antioxidant and Anti-Inflammatory Activities of Essential Oils: A Short Review
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- Authors
- Yoshimura, A.
- Affiliations
- Kyushu University (JP)
- Corresponding author
- Yoshimura, Akihiko
- ORCID
- Yoshimura, Akihiko
- Venue
- Cancer Science
- Publisher
- Wiley
- Published
- 2006-03-31
- Volume
- 97
- Issue
- 6
- Pages
- 439-447
- ISSN
- 1347-9032 (ISSN-L)
- 1349-7006
- PMC
- PMC11159428
- OpenAlex
- W2130156594
- Cited by
- 314
- References
- 65
- Citations by year
- 2026: 3 · 2025: 7 · 2024: 8 · 2023: 17 · 2022: 9 · 2021: 6 · 2020: 14 · 2019: 9 · 2018: 12 · 2017: 14 · 2016: 12 · 2015: 16 · 2014: 20 · 2013: 22 · 2012: 29
- FWCI
- 2.19
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Cancer Science (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Oncology › Cytokine Signaling Pathways and Interactions
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › NF-κB Signaling Pathways
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Signaling Pathways in Disease
- Keywords
- inflammatory cytokines, signal transduction, inflammation-associated carcinogenesis, TNF-α, interferon-gamma, interleukin-6, NF-κB, STAT1, STAT3, transcription factors, apoptosis, macrophages, NF-κB inhibition, tumor regression
- MeSH terms
- Animals, Cell Transformation, Neoplastic, Humans, Inflammation, Macrophages, Signal Transduction, Cytokines
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