Oncogenic Activation of NF- B
Open accessAbstract
Recent genetic evidence has established a pathogenetic role for NF-kappaB signaling in cancer. NF-kappaB signaling is engaged transiently when normal B lymphocytes respond to antigens, but lymphomas derived from these cells accumulate genetic lesions that constitutively activate NF-kappaB signaling. Many genetic aberrations in lymphomas alter CARD11, MALT1, or BCL10, which constitute a signaling complex that is intermediate between the B-cell receptor and IkappaB kinase. The activated B-cell-like subtype of diffuse large B-cell lymphoma activates NF-kappaB by a variety of mechanisms including oncogenic mutations in CARD11 and a chronic active form of B-cell receptor signaling. Normal plasma cells activate NF-kappaB in response to ligands in the bone marrow microenvironment, but their malignant counterpart, multiple myeloma, sustains a variety of genetic hits that stabilize the kinase NIK, leading to constitutive activation of the classical and alternative NF-kappaB pathways. Various oncogenic abnormalities in epithelial cancers, including mutant K-ras, engage unconventional IkappaB kinases to activate NF-kappaB. Inhibition of constitutive NF-kappaB signaling in each of these cancer types induces apoptosis, providing a rationale for the development of NF-kappaB pathway inhibitors for the treatment of cancer.
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A number of NF-κB-targeting drugs have been used in clinical trials, with sometimes disappointing results.
“A number of NF-κB-targeting drugs have been used in clinical trials, with sometimes disappointing results (45).”
From Tumor suppressor PDCD4 inhibits NF-κB-dependent transcription in human glioblastoma cells by direct interaction with p65 (2014) · cites this paper as [45]
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- Authors
- Staudt, L. M.
- Affiliations
- National Institutes of Health (US)
- Corresponding author
- Staudt, L. M.
- ORCID
- Staudt, L. M.
- Venue
- Cold Spring Harbor Perspectives in Biology
- Publisher
- Cold Spring Harbor Laboratory
- Published
- 2010-04-21
- Volume
- 2
- Issue
- 6
- Pages
- a000109-a000109
- ISSN
- 1943-0264 (ISSN-L)
- PMC
- PMC2869521
- OpenAlex
- W2020045401
- Cited by
- 485
- References
- 2
- Citations by year
- 2026: 12 · 2025: 19 · 2024: 16 · 2023: 13 · 2022: 23 · 2021: 22 · 2020: 23 · 2019: 32 · 2018: 40 · 2017: 22 · 2016: 37 · 2015: 53 · 2014: 46 · 2013: 32 · 2012: 34
- Type
- posted content
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Cold Spring Harbor Perspectives in Biology (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health
- National Cancer Institute
- Topics
- 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
- Health Sciences › Medicine › Pathology and Forensic Medicine › Lymphoma Diagnosis and Treatment
- Keywords
- NF-κB signaling, oncogene activation, lymphoma, diffuse large B-cell lymphoma, activated B-cell-like subtype, CARD11, MALT1, BCL10, B cell receptor signaling, multiple myeloma, NIK, IκB kinase, KRAS mutation, epithelial cancers, apoptosis, NF-κB inhibitors
- MeSH terms
- Animals, Antineoplastic Agents, Humans, Signal Transduction, Gene Expression Regulation, Neoplastic, NF-kappa B
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