NF-κB links innate immunity to the hypoxic response through transcriptional regulation of HIF-1α

By J. Rius, Mónica Gumá, C. Schachtrup, K. Akassoglou, A. Zinkernagel, V. Nizet, Richard J. Johnson, G. Haddad, M. Karin. Nature, 2008

1,449 citations recorded by the source corpus.

Subfields: Cancer Research, Immunology

View Paper: https://www.semanticscholar.org/paper/6cc87199dae4cda8bb228f2f548d6ef6bbb9a5c1

How researchers see this paper

The researchers whose trusted networks rank it highest, strongest advocate first. Every researcher gets a different order.

In Cancer Research

1. A. Mantovani
2. S. Grivennikov
3. M. Karin
4. V. Nizet
5. A. Sica
6. M. Nieto
7. F. Balkwill
8. P. Allavena

In Immunology

1. A. Mantovani
2. A. Sica
3. M. Karin
4. P. Allavena
5. F. Balkwill
6. C. Garlanda
7. S. Grivennikov
8. F. Colotta

Citations in the corpus

• Dangerous liaisons: STAT3 and NF-κB collaboration and crosstalk in cancer (2009, background): “NF-kB was also shown to be an important regulator of HIF1a gene transcription and a regulator of VEGF gene expression [82], although it remains to be proven experimentally whether NF-kB directly activates VEGF gene expression or it does so via induction of HIF1a, which is a direct activation of VEGF”
• Immunity, Inflammation, and Cancer (2010, neutral): “Important proangiogenic genes, such as IL-8, CXCL1, CXCL8, VEGF, and hypoxia-inducible factor 1 alpha (HIF1a), are directly regulated by NF-kB, STAT3, and AP-1 in TAMs, MDSCs, and other cell types (Kujawski et al., 2008; Rius et al., 2008).”
• Interdependence of hypoxic and innate immune responses (2009, methodology): “The activation of Hif1a transcription by bacteria or LPS under normoxic as well as hypoxic conditions has been recently verified in a study using mice deficient in IKK&beta”
• Cancer as a metabolic disease (2010, background): “under aerobic conditions can be linked to mitochondrial dysfunction through abnormalities in calcium homeostasis, ROS generation, NFkB signaling, accumulation of TCA cycle metabolites (succinate and fumarate), and oncogenic viral infections [131-135].”
• The ins and outs of the epithelial to mesenchymal transition in health and disease. (2011, background): “Signals released in response to inflammation, oxidative stress, and hypoxia in the stromal or interstitial cells in tumors or fibrotic tissues (TAMs, CAFs, leukocytes, and myofibroblasts) converge in the activation of NF-κB, a potent inducer of EMT.”
• Cancer-related inflammation, the seventh hallmark of cancer: links to genetic instability. (2009, background): “Key orchestrators at the intersection of the intrinsic and extrinsic pathway include transcription factors and primary pro-inflammatory cytokines [7,8].”
• Different tumor microenvironments contain functionally distinct subsets of macrophages derived from Ly6C(high) monocytes. (2010, background): “Interestingly, a recent report showed that IKKβ is required for HIF-1α accumulation under hypoxic conditions, thereby uncovering a link between the hypoxic response and NF-κB (40).”
• The Metabolic Signature of Macrophage Responses (2019, background): “Excess of succinate leads to Hypoxia Inducible Factor 1α (HIF1α) stabilization that, in turn, activates the transcription of glycolytic genes, thus sustaining the glycolytic metabolism of M1 macrophages.”
• Cancer-related inflammation (2008, background): “There is also accumulating evidence of interconnections and compensatory pathways between the NF-κB and HIF1α system”
• Tumor cell biodiversity drives microenvironmental reprogramming in liver cancer (2019, background): “Mechanistically, PI3K/AKT and NF-κB pathways have been demonstrated to be responsible for induction of hypoxia-induced HIF1A mRNA expression (Belaiba et al., 2007; Rius et al., 2008).”
• Regulation of cell signalling by uPAR (2010, background): “Nuclear factor-κB (NF-κB) also activates uPAR expression, either indirectly through HIF1”
• The importance of antioxidants which play the role in cellular response against oxidative/nitrosative stress: current state (2015, background): “Another NF-kB target gene that contributes to both survival and innate immune functions is the HIF-1α gene, encoding the oxygen-regulated subunit of the hypoxia responsive transcription factor HIF-1 [101].”