ArticleProceedings of the National Academy of Sciences of the United States of America2013
Met synergizes with p53 loss to induce mammary tumors that possess features of claudin-low breast cancer.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 50 papers, 1 of them a synthesis that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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
50 citing papers in PubMed, 1 synthesis or guideline pooled it, 73 citations in OpenAlex.
- Comparative oncogenomics identifies combinations of driver genes and drug targets in BRCA1-mutated breast cancer.Nature communications · 2019Pooled it
- C-MET tyrosine kinase receptor: mechanisms, clinical applications and future perspectives in cancer therapy.Signal transduction and targeted therapy · 2026Review
- Insights from Genomic Sequencing of Preclinical Breast Cancer Models Establish Human Parallels to Increase Therapeutic Applicability.Journal of mammary gland biology and neoplasia · 2026Review
- Multi-omics profiling uncovers immune-molecular clusters with distinct chemo-immunotherapeutic vulnerabilities in a mouse model of triple-negative breast cancer.Molecular cancer · 2026Article
- Murine models for triple-negative breast cancer with differential responsiveness to immunotherapy.Journal of translational research · 2026Article
- Reactivation of Multipotency in the Mammary Gland - a Ripple in the Pond and a Turn of the Tide.Journal of mammary gland biology and neoplasia · 2025Review
- Review
- 2-methoxyestradiol inhibits the malignant behavior of triple negative breast cancer cells by altering their miRNome.Frontiers in oncology · 2024Article
- FRA-1 as a Regulator of EMT and Metastasis in Breast Cancer.International journal of molecular sciences · 2023Review
- Research progress of Claudin-low breast cancer.Frontiers in oncology · 2023Review
- Mammary-specific expression of Trim24 establishes a mouse model of human metaplastic breast cancer.Nature communications · 2021Article
- Single allele loss-of-function mutations select and sculpt conditional cooperative networks in breast cancer.Nature communications · 2021Article
- Co-dependency for MET and FGFR1 in basal triple-negative breast cancers.NPJ breast cancer · 2021Article
- OMO-1 reduces progression and enhances cisplatin efficacy in a 4T1-based non-c-MET addicted intraductal mouse model for triple-negative breast cancer.NPJ breast cancer · 2021Article
- The p53-inducible CLDN7 regulates colorectal tumorigenesis and has prognostic significance.Neoplasia (New York, N.Y.) · 2020Article
- Targeting c-Met in triple negative breast cancer: preclinical studies using the c-Met inhibitor, Cpd A.Investigational new drugs · 2020Article
- Dichotomous roles of claudins as tumor promoters or suppressors: lessons from knockout mice.Cellular and molecular life sciences : CMLS · 2019Review
- p53 controls the plasticity of mammary luminal progenitor cells downstream of Met signaling.Breast cancer research : BCR · 2019Article
- HGF-induced migration depends on the PI(3,4,5)PThe Journal of cell biology · 2019Article
- Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
18 authors at 7 institutions in 2 countries.
Funding
Abstract
Triple-negative breast cancer (TNBC) accounts for ∼20% of cases and contributes to basal and claudin-low molecular subclasses of the disease. TNBCs have poor prognosis, display frequent mutations in tumor suppressor gene p53 (TP53), and lack targeted therapies. The MET receptor tyrosine kinase is elevated in TNBC and transgenic Met models (Met(mt)) develop basal-like tumors. To investigate collaborating events in the genesis of TNBC, we generated Met(mt) mice with conditional loss of murine p53 (Trp53) in mammary epithelia. Somatic Trp53 loss, in combination with Met(mt), significantly increased tumor penetrance over Met(mt) or Trp53 loss alone. Unlike Met(mt) tumors, which are histologically diverse and enriched in a basal-like molecular signature, the majority of Met(mt) tumors with Trp53 loss displayed a spindloid pathology with a distinct molecular signature that resembles the human claudin-low subtype of TNBC, including diminished claudins, an epithelial-to-mesenchymal transition signature, and decreased expression of the microRNA-200 family. Moreover, although mammary specific loss of Trp53 promotes tumors with diverse pathologies, those with spindloid pathology and claudin-low signature display genomic Met amplification. In both models, MET activity is required for maintenance of the claudin-low morphological phenotype, in which MET inhibitors restore cell-cell junctions, rescue claudin 1 expression, and abrogate growth and dissemination of cells in vivo. Among human breast cancers, elevated levels of MET and stabilized TP53, indicative of mutation, correlate with highly proliferative TNBCs of poor outcome. This work shows synergy between MET and TP53 loss for claudin-low breast cancer, identifies a restricted claudin-low gene signature, and provides a rationale for anti-MET therapies in TNBC.
Indexed as
Identifiers
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.