ArticleCell death & disease2015
Targeting Mdmx to treat breast cancers with wild-type p53.
Article in Cell death & disease, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.
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Who cites it
31 citing papers in PubMed, 43 citations in OpenAlex.
- Uncovering immune cell-associated genes in breast cancer: based on summary data-based Mendelian randomized analysis and colocalization study.Breast cancer research : BCR · 2024Article
- Identification and validation of the biomarkers related to ferroptosis in calcium oxalate nephrolithiasis.Aging · 2024Article
- p53 Dysregulation in Breast Cancer: Insights on Mutations in theInternational journal of molecular sciences · 2023Article
- MDMX elevation by a novel Mdmx-p53 interaction inhibitor mitigates neuronal damage after ischemic stroke.Scientific reports · 2022Article
- MDMX Regulates Transcriptional Activity of p53 and FOXO Proteins to Stimulate Proliferation of Melanoma Cells.Cancers · 2022Article
- Targeting MDM4 as a Novel Therapeutic Approach in Prostate Cancer Independent of p53 Status.Cancers · 2022Article
- BRD7 Stabilizes P53 via Dephosphorylation of MDM2 to Inhibit Tumor Growth in Breast Cancer Harboring Wild-type P53.Journal of Cancer · 2022Article
- Hesperidin Inhibits the p53-MDMXInteraction-Induced Apoptosis of Non-Small-Cell Lung Cancer and Enhances the Antitumor Effect of Carboplatin.Journal of oncology · 2022Article
- Article
- First in class dual MDM2/MDMX inhibitor ALRN-6924 enhances antitumor efficacy of chemotherapy in TP53 wild-type hormone receptor-positive breast cancer models.Breast cancer research : BCR · 2021Article
- Associations ofJournal of clinical medicine · 2021Article
- Inflammatory Breast Cancer: Clinical Implications of Genomic Alterations and Mutational Profiling.Cancers · 2020Article
- CDK9 activity is critical for maintaining MDM4 overexpression in tumor cells.Cell death & disease · 2020Article
- Fine-mapping of 150 breast cancer risk regions identifies 191 likely target genes.Nature genetics · 2020Article
- Identification of Potential Prognostic Biomarkers for Breast Cancer Based on lncRNA-TF-Associated ceRNA Network and Functional Module.BioMed research international · 2020Article
- Frequent amplifications of ESR1, ERBB2 and MDM4 in primary invasive lobular breast carcinoma.Cancer letters · 2019Article
- Regulation of PRMT5-MDM4 axis is critical in the response to CDK4/6 inhibitors in melanoma.Proceedings of the National Academy of Sciences of the United States of America · 2019Article
- Specific allelic variants of SNPs in theOncotarget · 2019Article
- The long and the short of it: the MDM4 tail so far.Journal of molecular cell biology · 2019Review
- Context-dependent roles of MDMX (MDM4) and MDM2 in breast cancer proliferation and circulating tumor cells.Breast cancer research : BCR · 2019Article
Corrections and comments
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Authors and funding
16 authors at 5 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The function of the tumor suppressor p53 is universally compromised in cancers. It is the most frequently mutated gene in human cancers (reviewed). In cases where p53 is not mutated, alternative regulatory pathways inactivate its tumor suppressive functions. This is primarily achieved through elevation in the expression of the key inhibitors of p53: Mdm2 or Mdmx (also called Mdm4) (reviewed). In breast cancer (BrCa), the frequency of p53 mutations varies markedly between the different subtypes, with basal-like BrCas bearing a high frequency of p53 mutations, whereas luminal BrCas generally express wild-type (wt) p53. Here we show that Mdmx is unexpectedly highly expressed in normal breast epithelial cells and its expression is further elevated in most luminal BrCas, whereas p53 expression is generally low, consistent with wt p53 status. Inducible knockdown (KD) of Mdmx in luminal BrCa MCF-7 cells impedes the growth of these cells in culture, in a p53-dependent manner. Importantly, KD of Mdmx in orthotopic xenograft transplants resulted in growth inhibition associated with prolonged survival, both in a preventative model and also in a treatment model. Growth impediment in response to Mdmx KD was associated with cellular senescence. The growth inhibitory capacity of Mdmx KD was recapitulated in an additional luminal BrCa cell line MPE600, which expresses wt p53. Further, the growth inhibitory capacity of Mdmx KD was also demonstrated in the wt p53 basal-like cell line SKBR7 line. These results identify Mdmx growth dependency in wt p53 expressing BrCas, across a range of subtypes. Based on our findings, we propose that Mdmx targeting is an attractive strategy for treating BrCas harboring wt p53.
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