ArticleAmerican journal of cancer research2020
Bis-indole derived nuclear receptor 4A1 (NR4A1) antagonists inhibit TGFβ-induced invasion of embryonal rhabdomyosarcoma cells.
Article in American journal of cancer research, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.
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Who cites it
10 citing papers in PubMed, 11 citations in OpenAlex.
- Murine toxicology assessment of avgn7.2, a novel gene therapeutic for inclusion body myositis and other muscle wasting diseases.Gene therapy · 2026Article
- Perfluorooctane Sulfonate (PFOS) and Related Compounds Induce Nuclear Receptor 4A1 (NR4A1)-Dependent Carcinogenesis.Chemical research in toxicology · 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
- A novel NR4A2-HuR axis promotes pancreatic cancer growth and tumorigenesis that is inhibited by NR4A2 antagonists.American journal of cancer research · 2024Article
- Natural compounds targeting nuclear receptors for effective cancer therapy.Cancer metastasis reviews · 2023Review
- Nr4a1 promotes renal interstitial fibrosis by regulating the p38 MAPK phosphorylation.Molecular medicine (Cambridge, Mass.) · 2023Article
- NR4A1 Promotes LPS-Induced Acute Lung Injury through Inhibition of Opa1-Mediated Mitochondrial Fusion and Activation of PGAM5-Related Necroptosis.Oxidative medicine and cellular longevity · 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
- Repurposing of posaconazole as a hedgehog/SMO signaling inhibitor for embryonal rhabdomyosarcoma therapy.American journal of cancer research · 2021Article
Corrections and comments
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
Transforming growth factor β (TGFβ) enhances invasion of breast and lung cancer cells through phosphorylation-dependent nuclear export of the nuclear receptor 4A1 (NR4A1, Nur77). This response is inhibited by the NR4A1 antagonist 1,1-bis(3'-indoly)-1-(p-hydroxyphenyl) methane (CDIM8) and we hypothesized that similar effects would be observed in Rhabdomyosarcoma (RMS) cells. Although some kinase inhibitors block TGFβ-induced invasion of embryonal RMS (ERMS) cells, the mechanism differs from breast and lung cancer cells since NR4A1 is extranuclear in ERMS cells. However, CDIM8 blocks basal and TGFβ-induced invasion of RD and SMS-CTR ERMS cell lines but not Rh30 alveolar RMS (ARMS) cells. Moreover, this response in ERMS cells was independent of SMAD7 degradation or activation of SMAD2/SMAD3. β-Catenin silencing decreased ERMS cell invasion and CDIM8 induced proteasome-independent downregulation of β-catenin. The novel mechanism of CDIM8-mediated inhibition of basal and TGFβ-induced ERMS cell invasion was due to activation of the Bcl-2-NR4A1 complex, mitochondrial disruption, induction of the tumor suppressor-like cytokine interleukin-24 (IL-24) which in turn downregulates β-catenin expression. Thus, the NR4A1 antagonist inhibits TGFβ-induced invasion of ERMS cells through initial targeting of cytosolic NR4A1.
Indexed as
Identifiers
32905449PMC7471359W3086856895What 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.