ArticleThe Journal of experimental medicine2013
Modulation of NKG2D ligand expression and metastasis in tumors by spironolactone via RXRγ activation.
Article in The Journal of experimental medicine, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 38 papers, 1 of them a synthesis that pooled it.
What it found
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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
38 citing papers in PubMed, 1 synthesis or guideline pooled it, 57 citations in OpenAlex.
- Tumor risks of finerenone in patients with type 2 diabetes mellitus complicated with chronic kidney disease: a meta-analysis and systematic review of randomized controlled trials.Frontiers in pharmacology · 2023Pooled it
- NKGD2 Ligands (NKG2DLs) in Breast Cancer: In Silico Analysis and Narrative Review.International journal of molecular sciences · 2026Review
- Spironolactone Targets Retinoid X Receptor γ to Promote Myelin Sheath Regeneration.Neurology(R) neuroimmunology & neuroinflammation · 2025Article
- FEV-mediated WNT2 transcription is involved in the progression of colorectal cancer via the Wnt signaling.Cytotechnology · 2024Article
- Cancer Development and Progression in Patients with Heart Failure.Current heart failure reports · 2024Review
- Heart failure pharmacotherapy and cancer: pathways and pre-clinical/clinical evidence.European heart journal · 2024Review
- Efbalropendekin Alfa enhances human natural killer cell cytotoxicity against tumor cell linesFrontiers in immunology · 2024Article
- Lenalidomide improves NKG2D-based CAR-T cell activity against colorectal cancer cells invitro.Heliyon · 2023Article
- Immunosuppressive mesenchymal stem cells aggregates incorporating hydrogel microspheres promote an in vitro invasion of cancer cells.Regenerative therapy · 2021Article
- Topical Treatment of Human Skin and Cultured Keratinocytes with High-Dose Spironolactone Reduces XPB Expression and Induces Toxicity.JID innovations : skin science from molecules to population health · 2021Article
- Genome-scale screens identify factors regulating tumor cell responses to natural killer cells.Nature genetics · 2021Article
- CAR-NK Cells in the Treatment of Solid Tumors.International journal of molecular sciences · 2021Review
- The Use of Antihypertensive Drugs as Coadjuvant Therapy in Cancer.Frontiers in oncology · 2021Review
- Review
- [Overexpression of NKG2D-CD3ζ in NY-ESO-1 TCR-T cells enhanced cytotoxicity to acute myeloid leukemia cellsZhonghua xue ye xue za zhi = Zhonghua xueyexue zazhi · 2020Article
- A novel treatment for skin repair using a combination of spironolactone and vitamin D3.Annals of the New York Academy of Sciences · 2020Article
- Spironolactone and XPB: An Old Drug with a New Molecular Target.Biomolecules · 2020Review
- Unleashing Natural Killer Cells in the Tumor Microenvironment-The Next Generation of Immunotherapy?Frontiers in immunology · 2020Review
- T cells expressing NKG2D chimeric antigen receptors efficiently eliminate glioblastoma and cancer stem cells.Journal for immunotherapy of cancer · 2019Article
- Spironolactone inhibits the growth of cancer stem cells by impairing DNA damage response.Oncogene · 2019Article
Corrections and comments
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
Abstract
Tumor metastasis and lack of NKG2D ligand (NKG2DL) expression are associated with poor prognosis in patients with colon cancer. Here, we found that spironolactone (SPIR), an FDA-approved diuretic drug with a long-term safety profile, can up-regulate NKG2DL expression in multiple colon cancer cell lines by activating the ATM-Chk2-mediated checkpoint pathway, which in turn enhances tumor elimination by natural killer cells. SPIR can also up-regulate the expression of metastasis-suppressor genes TIMP2 and TIMP3, thereby reducing tumor cell invasiveness. Although SPIR is an aldosterone antagonist, its antitumor effects are independent of the mineralocorticoid receptor pathway. By screening the human nuclear hormone receptor siRNA library, we identified retinoid X receptor γ (RXRγ) instead as being indispensable for the antitumor functions of SPIR. Collectively, our results strongly support the use of SPIR or other RXRγ agonists with minimal side effects for colon cancer prevention and therapy.
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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.