ArticleGynecologic oncology2019
Nuclear receptor 4A1 (NR4A1) antagonists induce ROS-dependent inhibition of mTOR signaling in endometrial cancer.
Article in Gynecologic oncology, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed, 24 citations in OpenAlex.
- PROTAC-mediated targeting of IKKβ and NR4A1 for AML therapy.Oncogene · 2026Article
- Orphan nuclear receptor 4A1 (NR4A1) and NR4A2 are endogenous regulators of CD71 and their ligands induce ferroptosis in breast cancer.Cell death & disease · 2025Article
- Article
- Natural products and synthetic analogs as selective orphan nuclear receptor 4A (NR4A) modulators.Histology and histopathology · 2024Review
- Thioredoxin Domain Containing 5 (TXNDC5): Friend or Foe?Current issues in molecular biology · 2024Review
- A novel NR4A2-HuR axis promotes pancreatic cancer growth and tumorigenesis that is inhibited by NR4A2 antagonists.American journal of cancer research · 2024Article
- Flavonoids Quercetin and Kaempferol Are NR4A1 Antagonists and Suppress Endometriosis in Female Mice.Endocrinology · 2023Article
- Targeting intracellular proteins with cell type-specific functions for cancer immunotherapy.Life medicine · 2023Review
- Piperlongumine is a ligand for the orphan nuclear receptor 4A1 (NR4A1).Frontiers in pharmacology · 2023Article
- Therapeutic potential of NR4A1 in cancer: Focus on metabolism.Frontiers in oncology · 2022Review
- Nuclear receptor 4A1 (NR4A1) antagonists target paraspeckle component 1 (PSPC1) in cancer cells.Molecular carcinogenesis · 2022Article
- Orphan nuclear receptor 4A1 (NR4A1) and novel ligands.Essays in biochemistry · 2021Article
- Flavonoids kaempferol and quercetin are nuclear receptor 4A1 (NR4A1, Nur77) ligands and inhibit rhabdomyosarcoma cell and tumor growth.Journal of experimental & clinical cancer research : CR · 2021Article
- The Histone Methyltransferase Gene G9A Is Regulated by Nuclear Receptor 4A1 in Alveolar Rhabdomyosarcoma Cells.Molecular cancer therapeutics · 2021Article
- The Paradoxical Roles of Orphan Nuclear Receptor 4A (NR4A) in Cancer.Molecular cancer research : MCR · 2021Review
- Advanced oxidation protein products change biological behaviors of rat endometrial epithelial cells by activating ERK/P38 signaling pathways.Biology open · 2020Article
- Bis-Indole-Derived Nuclear Receptor 4A1 (NR4A1, Nur77) Ligands as Inhibitors of Endometriosis.Endocrinology · 2020Article
- A Bis-Indole-Derived NR4A1 Antagonist Induces PD-L1 Degradation and Enhances Antitumor Immunity.Cancer research · 2020Article
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5 authors at 1 institution in 1 country.
Funding
Abstract
objectivesNR4A1 is overexpressed in many solid tumors, and the objectives of this study were to investigate the expression and functional role of this receptor in endometrial cancer cells and demonstrate that NR4A1 antagonist inhibit mTOR.
methodsIshikawa and Hec-1B endometrial cells were used as models to investigate the parallel effects of NR4A1 knockdown by RNA interference (siNR4A1) and treatment with bis-indole-derived NR4A1 ligands (antagonists) on cell growth and survival by determining cell numbers and effects on Annexin V staining. Western blot analysis of whole cell lysates was used to determine effects of these treatments on expression of growth promoting, survival and apoptotic genes and mTOR signaling. Effects of NR4A1 antagonists on tumor growth were determined in athymic nude mice bearing Hec-1B cells as xenografts.
resultssiNR4A1 or treatment with bis-indole-derived NR4A1 antagonists inhibited growth of endometrial cancer cells in vitro and endometrial tumors in vivo and this was accompanied by decreased expression of growth promoting and survival genes and mTOR inhibition.
conclusionsNR4A1 exhibited pro-oncogenic activity in endometrial cells due, in part, to regulation of cell growth, survival and mTOR signaling, and all of these pathways and their associated gene products were inhibited after treatment with bis-indole-derived NR4A1 antagonists. Moreover, these compounds also blocked endometrial tumor growth in vivo demonstrating that NR4A1 is a potential novel drug target for treatment of endometrial cancer.
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