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Targeting NR4A nuclear receptors to control stromal cell inflammation, metabolism, angiogenesis, and tumorigenesis

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dc.contributor.author Crean, Daniel
dc.contributor.author Murphy, Evelyn P.
dc.date.accessioned 2021-03-03T11:09:16Z
dc.date.available 2021-03-03T11:09:16Z
dc.date.issued 2021
dc.identifier.uri http://hdl.handle.net/10344/9837
dc.description peer-reviewed en_US
dc.description.abstract The NR4A1–NR4A3 (Nur77, Nurr1, and Nor-1) subfamily of nuclear receptors is a group of immediate early genes induced by a pleiotropy of stimuli including peptide hormones, growth factors, cytokines, inflammatory, and physiological stimuli, and cellular stress. NR4A receptors function as potent sensors of changes in the cellular microenvironment to control physiological and pathological processes through genomic and non-genomic actions. NR4A receptors control metabolism and cardiovascular and neurological functions and mediate immune cell homeostasis in inflammation and cancer. This receptor subfamily is increasingly recognized as an important molecular connection between chronic inflammation, altered immune cell responses, and cancer development. In this review, we examine how transcriptome analysis identified NR4A1/NR4A2 receptors as transcriptional regulators in mesenchymal stromal cell (MSC) migration, cell cycle progression, and cytokine production to control local immune responses. In chronic inflammatory conditions, such as rheumatoid arthritis, NR4A receptors have been shown to modify the activity of MSC and fibroblast-like stromal cells to regulate synovial tissue hyperplasia, pathological angiogenesis, and cartilage turnover in vivo. Additionally, as NR4A1 has been observed as a major transcriptional regulator in tumor–stromal communication controlling tumorigenesis, we discuss how advances in the pharmacological control of these receptors lead to important new mechanistic insights into understanding the role of the tumor microenvironment in health and disease. en_US
dc.language.iso eng en_US
dc.publisher Frontiers Media en_US
dc.relation.ispartofseries Frontiers in Cell and Developmental;9, 589770
dc.subject Receptors en_US
dc.subject pharmacological control en_US
dc.subject mechanistic en_US
dc.subject inflammatory homeostasis en_US
dc.title Targeting NR4A nuclear receptors to control stromal cell inflammation, metabolism, angiogenesis, and tumorigenesis en_US
dc.type info:eu-repo/semantics/article en_US
dc.type.supercollection all_ul_research en_US
dc.type.supercollection ul_published_reviewed en_US
dc.identifier.doi 10.3389/fcell.2021.589770
dc.contributor.sponsor School of Medicine, University Limerick en_US
dc.rights.accessrights info:eu-repo/semantics/openAccess en_US


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