ArticleBiochemical and biophysical research communications2009
TNFalpha induces HIF-1alpha expression through activation of IKKbeta.
Article in Biochemical and biophysical research communications, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 27 citations in OpenAlex.
- Unraveling the role of HIF-1α in sepsis: from pathophysiology to potential therapeutics-a narrative review.Critical care (London, England) · 2024Review
- Interferons Are Pro-Inflammatory Cytokines in Sheared-Stressed Human Aortic Valve Endothelial Cells.International journal of molecular sciences · 2021Article
- Nicotinamide riboside, an NADLaboratory investigation; a journal of technical methods and pathology · 2021Article
- Article
- IKKβ targeting reduces KRAS-induced lung cancer angiogenesis in vitro and in vivo: A potential anti-angiogenic therapeutic target.Lung cancer (Amsterdam, Netherlands) · 2019Article
- Expression levels of miR-143-3p and -424-5p in colorectal cancer and their clinical significance.Cancer biomarkers : section A of Disease markers · 2019Article
- Role of HIF-1α in Alcohol-Mediated Multiple Organ Dysfunction.Biomolecules · 2018Review
- Article
- NNC 55-0396, a T-type Ca2+ channel inhibitor, inhibits angiogenesis via suppression of hypoxia-inducible factor-1α signal transduction.Journal of molecular medicine (Berlin, Germany) · 2015Article
- Hypoxia-driven osteopontin contributes to breast tumor growth through modulation of HIF1α-mediated VEGF-dependent angiogenesis.Oncogene · 2014Article
- Molecular mechanisms underlying chronic inflammation-associated cancers.Cancer letters · 2014Review
- HIF-1 α had pivotal effects on downregulation of miR-210 decreasing viability and inducing apoptosis in hypoxic chondrocytes.TheScientificWorldJournal · 2014Article
- The biological kinship of hypoxia with CSC and EMT and their relationship with deregulated expression of miRNAs and tumor aggressiveness.Biochimica et biophysica acta · 2012Review
- The NFκB pathway: a therapeutic target in glioblastoma.Oncotarget · 2011Review
- Hypoxia-induced microRNA-424 expression in human endothelial cells regulates HIF-α isoforms and promotes angiogenesis.The Journal of clinical investigation · 2010Article
- Antibody treatment promotes compensation for human cytomegalovirus-induced pathogenesis and a hypoxia-like condition in placentas with congenital infection.The American journal of pathology · 2010Article
Corrections and comments
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Authors and funding
5 authors at 3 institutions in 2 countries.
Funding
Abstract
The transcription factor hypoxia-inducible factor 1alpha (HIF-1alpha) is regulated by oxygen availability as well as various inflammatory mediators, including tumor necrosis factor alpha (TNFalpha). Early work suggested that the phosphatidylinositol-3-kinase (PI3K) and mitogen-activated protein kinase (MAPK) signaling pathways are involved in TNFalpha-mediated HIF-1alpha accumulation and activation under normoxic conditions. Here, we provide evidence showing that IkappaB kinase beta (IKKbeta) is required for HIF-1alpha regulation by TNFalpha. We found that TNFalpha enhances HIF-1alpha protein expression in various breast cancer cell lines under either normoxic or hypoxia-mimicking conditions, but has little effect on the HIF-1alpha mRNA level. Increased HIF-1alpha expression was found in IKKbeta stable clones and transient transfectants, and depletion of IKKbeta consistently reduced the amount of HIF-1alpha protein. Treatment of cells with the IKKbeta inhibitor Bay 11-7082 reduced the TNFalpha-induced HIF-1alpha expression, suggesting that IKKbeta is required in this signaling pathway. Decreased expression of vascular endothelial growth factor (VEGF), a direct target of HIF-1alpha, was shown in IKKbeta-knockout mouse embryonic fibroblast cells. We further demonstrated a positive correlation between IKKbeta and VEGF expression in primary human breast cancer specimens. Our findings indicate that TNFalpha-induced HIF-1alpha accumulation is IKKbeta dependent, and may enable further understanding of the HIF-1alpha regulation by inflammatory signals.
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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.