ArticleMolecular cancer research : MCR2014
The orphan nuclear receptor NR4A1 (Nur77) regulates oxidative and endoplasmic reticulum stress in pancreatic cancer cells.
Article in Molecular cancer research : MCR, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 74 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
74 citing papers in PubMed, 107 citations in OpenAlex.
- Article
- Integrated multi-omics analysis identifies and validates endoplasmic reticulum stress and mitophagy-related biomarkers in MASLD.Scientific reports · 2026Article
- Nr4a1 β-cell specific deletion impairs glucose tolerance in female mice.American journal of physiology. Endocrinology and metabolism · 2026Article
- Toxicological Response of the BEAS-2B Cell After Acute Exposure at the Air-Liquid Interface to Ethylbenzene and m-Xylene Alone and in Binary Mixtures.Journal of applied toxicology : JAT · 2025Article
- Neuroprotective role of Nigella Sativa seed oil in mitigating bisphenol a-induced neurodegeneration.Scientific reports · 2025Article
- 7,7-Bis(3-Indolyl)-Journal of microbiology and biotechnology · 2025Article
- Controversy and multiple roles of the solitary nucleus receptor Nur77 in disease and physiology.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2025Review
- Targeting the nuclear orphan receptor NR4A1: a key target in lung cancer progression and therapeutic resistance.Frontiers in oncology · 2025Review
- Chitosan Nanoparticles, a Novel Drug Delivery System to Transfer Squalene for Hepatocyte Stress Protection.ACS omega · 2024Article
- Parecoxib Enhances Resveratrol against Human Colorectal Cancer Cells through Akt and TXNDC5 Inhibition and MAPK Regulation.Nutrients · 2024Article
- TXNDC5 Plays a Crucial Role in Regulating Endoplasmic Reticulum Activity through Different ER Stress Signaling Pathways in Hepatic Cells.International journal of molecular sciences · 2024Article
- Thioredoxin Domain Containing 5 (TXNDC5): Friend or Foe?Current issues in molecular biology · 2024Review
- The role and mechanism of TXNDC5 in disease progression.Frontiers in immunology · 2024Review
- A novel NR4A2-HuR axis promotes pancreatic cancer growth and tumorigenesis that is inhibited by NR4A2 antagonists.American journal of cancer research · 2024Article
- Analysis of an antioxidative defence system of hydrogen peroxide-treated pancreatic islet-derived 1.1B4 cells and siRNA targeting NR4A3-treated cells by microarray.Redox report : communications in free radical research · 2023Article
- Bis-indole-derived NR4A1 antagonists inhibit colon tumor and splenic growth and T-cell exhaustion.Cancer immunology, immunotherapy : CII · 2023Article
- Shared Genes and Molecular Mechanisms between Nonalcoholic Fatty Liver Disease and Hepatocellular Carcinoma Established by WGCNA Analysis.Global medical genetics · 2023Article
- PEPseq quantifies transcriptome-wide changes in protein occupancy and reveals selective translational repression after translational stress.Nucleic acids research · 2023Article
- The molecular consequences of androgen activity in the human breast.Cell genomics · 2023Article
- HDAC1 disrupts the tricarboxylic acid (TCA) cycle through the deacetylation of Nur77 and promotes inflammation in ischemia-reperfusion mice.Cell death discovery · 2023Article
14 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
8 authors at 5 institutions in 2 countries.
Funding
Abstract
unlabelledNR4A1 (Nur77, TR3) is an orphan nuclear receptor that is overexpressed in pancreatic cancer and exhibits pro-oncogenic activity. RNA interference of NR4A1 expression in Panc-1 cells induced apoptosis and subsequent proteomic analysis revealed the induction of several markers of endoplasmic reticulum stress, including glucose-related protein 78 (GRP78), CCAAT/enhancer-binding protein-homologous protein (CHOP), and activating transcription factor-4 (ATF-4). Treatment of pancreatic cancer cells with the NR4A1 antagonist 1,1-bis(3'-indolyl)-1-(p-hydroxyphenyl)methane (DIM-C-pPhOH) gave similar results. Moreover, both NR4A1 knockdown and DIM-C-pPhOH induced reactive oxygen species (ROS), and induction of ROS and endoplasmic reticulum stress by these agents was attenuated after cotreatment with antioxidants. Manipulation of NR4A1 expression coupled with gene expression profiling identified a number of ROS metabolism transcripts regulated by NR4A1. Knockdown of one of these transcripts, thioredoxin domain containing 5 (TXNDC5), recapitulated the elevated ROS and endoplasmic reticulum stress; thus, demonstrating that NR4A1 regulates levels of endoplasmic reticulum stress and ROS in pancreatic cancer cells to facilitate cell proliferation and survival. Finally, inactivation of NR4A1 by knockdown or DIM-C-pPhOH decreased TXNDC5, resulting in activation of the ROS/endoplasmic reticulum stress and proapoptotic pathways. IMPLICATIONS: The NR4A1 receptor is pro-oncogenic, regulates the ROS/endoplasmic reticulum stress pathways, and inactivation of the receptor represents a novel pathway for inducing cell death in pancreatic cancer.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
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.