ArticleThe EMBO journal1997
Modulation of retinoic acid sensitivity in lung cancer cells through dynamic balance of orphan receptors nur77 and COUP-TF and their heterodimerization.
Article in The EMBO journal, 1997. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 50 papers.
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Who cites it
50 citing papers in PubMed, 160 citations in OpenAlex.
- NR4A1 and NR4A2 orphan nuclear receptors regulate endothelial-to-hematopoietic transition in mouse hematopoietic stem cell specification.Development (Cambridge, England) · 2024Article
- SIRT1 as a potential key regulator for mediating apoptosis in oropharyngeal cancer using cyclophosphamide and all-trans retinoic acid.Scientific reports · 2024Article
- International Union of Basic and Clinical Pharmacology CXIII: Nuclear Receptor Superfamily-Update 2023.Pharmacological reviews · 2023Review
- Targeting Nuclear Receptors in Lung Cancer-Novel Therapeutic Prospects.Pharmaceuticals (Basel, Switzerland) · 2022Review
- Retinoic Acids in the Treatment of Most Lethal Solid Cancers.Journal of clinical medicine · 2020Review
- New Insights in Cushing Disease Treatment With Focus on a Derivative of Vitamin A.Frontiers in endocrinology · 2018Review
- Honokiol sensitizes breast cancer cells to TNF-α induction of apoptosis by inhibiting Nur77 expression.British journal of pharmacology · 2016Article
- Role of histone deacetylases in pancreas: Implications for pathogenesis and therapy.World journal of gastrointestinal oncology · 2015Review
- The Orphan Nuclear Receptor NR4A1 Protects Pancreatic β-Cells from Endoplasmic Reticulum (ER) Stress-mediated Apoptosis.The Journal of biological chemistry · 2015Article
- Induction of Nur77 by hyperoside inhibits vascular smooth muscle cell proliferation and neointimal formation.Biochemical pharmacology · 2014Article
- COUP-TFII regulates metastasis of colorectal adenocarcinoma cells by modulating Snail1.British journal of cancer · 2014Article
- Further characterization of HDAC and SIRT gene expression patterns in pancreatic cancer and their relation to disease outcome.PloS one · 2014Article
- Multiple roles of COUP-TFII in cancer initiation and progression.Journal of molecular endocrinology · 2012Review
- Inhibition of β-catenin signaling by nongenomic action of orphan nuclear receptor Nur77.Oncogene · 2012Article
- NR4A gene expression is dynamically regulated in the ventral tegmental area dopamine neurons and is related to expression of dopamine neurotransmission genes.Journal of molecular neuroscience : MN · 2012Article
- Involvement of COUP-TFs in Cancer Progression.Cancers · 2011Article
- Targeting NR4A1 (TR3) in cancer cells and tumors.Expert opinion on therapeutic targets · 2011Review
- Retinoid pathway and cancer therapeutics.Advanced drug delivery reviews · 2010Review
- Induction and intracellular localization of Nur77 dictate fenretinide-induced apoptosis of human liver cancer cells.Biochemical pharmacology · 2010Article
- Potential of retinoic acid derivatives for the treatment of corticotroph pituitary adenomas.Reviews in endocrine & metabolic disorders · 2009Review
Corrections and comments
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Authors and funding
7 authors at 1 institution in 1 country.
Funding
Abstract
The diverse function of retinoic acid (RA) is mediated by its nuclear receptors, the retinoic acid receptors (RARs) and retinoid X receptors (RXRs). However, the RA response is often lost in cancer cells that express the receptors. Previously, it was demonstrated that the RA response is regulated by the COUP-TF orphan receptors. Here, we present evidence that nur77, another orphan receptor whose expression is highly induced by phorbol esters and growth factors, is involved in modulation of the RA response. Expression of nur77 enhances ligand-independent transactivation of RA response elements (RAREs) and desensitizes their RA responsiveness. Conversely, expression of COUP-TF sensitizes RA responsiveness of RAREs by repressing their basal transactivation activity. Unlike the effect of COUP-TFs, the function of nur77 does not require direct binding of nur77 to the RAREs, but is through interaction between nur77 and COUP-TFs. The interaction occurs in solution and results in inhibition of COUP-TF RARE binding and transcriptional activity. Unlike other nuclear receptors, a large portion of the carboxy-terminal end of nur77 is not required for its interaction with COUP-TF. In human lung cancer cell lines, COUP-TF is highly expressed in RA-sensitive cell lines while nur77 expression is associated with RA resistance. Stable expression of COUP-TF in nur77-positive, RA-resistant lung cancer cells enhances the inducibility of RARbeta gene expression and growth inhibition by RA. These observations demonstrate that a dynamic equilibrium between orphan receptors nur77 and COUP-TF, through their heterodimerization that regulates COUP-TF RARE binding, is critical for RA responsiveness of human lung cancer cells.
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