ArticleOncotarget2015
Inhibiting NFAT1 for breast cancer therapy: New insights into the mechanism of action of MDM2 inhibitor JapA.
Article in Oncotarget, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed, 26 citations in OpenAlex.
- Nuclear factor of activated T cells as a driver of tumor progression and a target for precision therapy.Animal models and experimental medicine · 2026Review
- Japonicone A and related dimeric sesquiterpene lactones: molecular targets and mechanisms of anticancer activity.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2022Review
- Perspectives on natural compounds in chemoprevention and treatment of cancer: an update with new promising compounds.European journal of cancer (Oxford, England : 1990) · 2021Review
- Targeting the p53-MDM2 pathway for neuroblastoma therapy: Rays of hope.Cancer letters · 2021Review
- Review
- Targeting MDM2 for novel molecular therapy: Beyond oncology.Medicinal research reviews · 2020Review
- Targeting β-Catenin Signaling by Natural Products for Cancer Prevention and Therapy.Frontiers in pharmacology · 2020Review
- The Trinity of Matrix Metalloproteinases, Inflammation, and Cancer: A Literature Review of Recent Updates.Anti-inflammatory & anti-allergy agents in medicinal chemistry · 2020Review
- Pyruvate Kinase M2: a Metabolic Bug in Re-Wiring the Tumor Microenvironment.Cancer microenvironment : official journal of the International Cancer Microenvironment Society · 2019Review
- Natural products targeting the p53-MDM2 pathway and mutant p53: Recent advances and implications in cancer medicine.Genes & diseases · 2018Review
- Therapeutic targeting of oncogenic transcription factors by natural products in eye cancer.Pharmacological research · 2018Review
- Inhibiting β-Catenin by β-Carboline-Type MDM2 Inhibitor for Pancreatic Cancer Therapy.Frontiers in pharmacology · 2018Article
- Highly efficient delivery of potent anticancer iminoquinone derivative by multilayer hydrogel cubes.Acta biomaterialia · 2017Article
- Novel natural product therapeutics targeting both inflammation and cancer.Chinese journal of natural medicines · 2017Review
- Targeting the NFAT1-MDM2-MDMX Network Inhibits the Proliferation and Invasion of Prostate Cancer Cells, Independent of p53 and Androgen.Frontiers in pharmacology · 2017Article
- Experimental Therapy of Advanced Breast Cancer: Targeting NFAT1-MDM2-p53 Pathway.Progress in molecular biology and translational science · 2017Review
- Oral delivery of anti-MDM2 inhibitor SP141-loaded FcRn-targeted nanoparticles to treat breast cancer and metastasis.Journal of controlled release : official journal of the Controlled Release Society · 2016Article
- Identification of lineariifolianoid A as a novel dual NFAT1 and MDM2 inhibitor for human cancer therapy.Journal of biomedical research · 2016Article
- Inulanolide A as a new dual inhibitor of NFAT1-MDM2 pathway for breast cancer therapy.Oncotarget · 2016Article
- Clinical Overview of MDM2/X-Targeted Therapies.Frontiers in oncology · 2016Review
Corrections and comments
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Authors and funding
6 authors at 4 institutions in 2 countries.
Funding
Abstract
Transcription factor NFAT1 has been recently identified as a new regulator of the MDM2 oncogene. Targeting the NFAT1-MDM2 pathway represents a novel approach to cancer therapy. We have recently identified a natural product MDM2 inhibitor, termed JapA. As a specific and potent MDM2 inhibitor, JapA inhibits MDM2 at transcriptional and post-translational levels. However, the molecular mechanism remains to be fully elucidated for its inhibitory effects on MDM2 transcription. Herein, we reported that JapA inhibited NFAT1 and NFAT1-mediated MDM2 transcription, which contributed to the anticancer activity of JapA. Its effects on the expression and activity of NFAT1 were examined in various breast cancer cell lines in vitro and in MCF-7 and MDA-MB-231 xenograft tumors in vivo. The specificity of JapA in targeting NFAT1 and NFAT1-MDM2 pathway and the importance of NFAT1 inhibition in JapA's anticancer activity were demonstrated using NFAT1 overexpression and knockdown cell lines and the pharmacological activators and inhibitors of NFAT1 signaling. Our results indicated that JapA inhibited NFAT1 signaling in breast cancer cells in vitro and in vivo, which plays a pivotal role in its anticancer activity. JapA inhibited the nuclear localization of NFAT1, disrupted the NFAT1-MDM2 P2 promoter complex, and induced NFAT1 proteasomal degradation, resulting in the repression of MDM2 transcription. In conclusion, JapA is a novel NFAT1 inhibitor and the NFAT1 inhibition is responsible for the JapA-induced repression of MDM2 transcription, contributing to its anticancer activity. The results may pave an avenue for validating the NFAT1-MDM2 pathway as a novel molecular target for cancer therapy.
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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.