ArticleThe Journal of clinical investigation2020
Deregulating MYC in a model of HER2+ breast cancer mimics human intertumoral heterogeneity.
Article in The Journal of clinical investigation, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.
What it found
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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.
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Who cites it
28 citing papers in PubMed, 52 citations in OpenAlex.
- Molecular life sciences in the era of the Fourth Industrial Revolution: sequencing, multi-omics and artificial intelligence.Emerging topics in life sciences · 2025Review
- Targeting MYC for the treatment of breast cancer: use of the novel MYC-GSPT1 degrader, GT19630.Investigational new drugs · 2025Article
- Integrated stress response plasticity governs normal cell adaptation to chronic stress via the PP2A-TFE3-ATF4 pathway.Cell death and differentiation · 2024Article
- Novel PP2A-Activating Compounds in Neuroblastoma.Cancers · 2024Article
- Bag-1-mediated HSF1 phosphorylation regulates expression of heat shock proteins in breast cancer cells.FEBS open bio · 2024Article
- A comprehensive overview of metaplastic breast cancer: Features and treatments.Cancer science · 2024Review
- Reciprocal interactions between lncRNAs and MYC in colorectal cancer: partners in crime.Cell death & disease · 2024Review
- Integrated stress response plasticity governs normal cell adaptation to chronic stress via the PP2A-TFE3-ATF4 pathway.Research square · 2024Article
- The Expression of Hsa-Mir-1225-5p Limits the Aggressive Biological Behaviour of Luminal Breast Cancer Cell Lines.MicroRNA (Shariqah, United Arab Emirates) · 2024Article
- Article
- MYC Deregulation and PTEN Loss Model Tumor and Stromal Heterogeneity of Aggressive Triple-Negative Breast Cancer.Nature communications · 2023Article
- Unraveling MYC's Role in Orchestrating Tumor Intrinsic and Tumor Microenvironment Interactions Driving Tumorigenesis and Drug Resistance.Pathophysiology : the official journal of the International Society for Pathophysiology · 2023Review
- Small-Molecule-Mediated Stabilization of PP2A Modulates the Homologous Recombination Pathway and Potentiates DNA Damage-Induced Cell Death.Molecular cancer therapeutics · 2023Article
- Changes of Mutations and Copy-Number and Enhanced Cell Migration during Breast Tumorigenesis.Advanced biology · 2023Article
- Article
- Co-targeting CDK2 and CDK4/6 overcomes resistance to aromatase and CDK4/6 inhibitors in ER+ breast cancer.NPJ precision oncology · 2022Article
- Review
- Single cell transcriptional diversity and intercellular crosstalk of human liver cancer.Cell death & disease · 2022Article
- Human epidermal growth factor receptor 2 (HER2)-specific chimeric antigen receptor (CAR) for tumor immunotherapy; recent progress.Stem cell research & therapy · 2022Review
- Dual Inhibition of Myc Transcription and PI3K Activity Effectively Targets Colorectal Cancer Stem Cells.Cancers · 2022Article
Corrections and comments
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Authors and funding
17 authors at 4 institutions in 2 countries.
Funding
Abstract
The c-MYC (MYC) oncoprotein is often overexpressed in human breast cancer; however, its role in driving disease phenotypes is poorly understood. Here, we investigate the role of MYC in HER2+ disease, examining the relationship between HER2 expression and MYC phosphorylation in HER2+ patient tumors and characterizing the functional effects of deregulating MYC expression in the murine NeuNT model of amplified-HER2 breast cancer. Deregulated MYC alone was not tumorigenic, but coexpression with NeuNT resulted in increased MYC Ser62 phosphorylation and accelerated tumorigenesis. The resulting tumors were metastatic and associated with decreased survival compared with NeuNT alone. MYC;NeuNT tumors had increased intertumoral heterogeneity including a subtype of tumors not observed in NeuNT tumors, which showed distinct metaplastic histology and worse survival. The distinct subtypes of MYC;NeuNT tumors match existing subtypes of amplified-HER2, estrogen receptor-negative human tumors by molecular expression, identifying the preclinical utility of this murine model to interrogate subtype-specific differences in amplified-HER2 breast cancer. We show that these subtypes have differential sensitivity to clinical HER2/EGFR-targeted therapeutics, but small-molecule activators of PP2A, the phosphatase that regulates MYC Ser62 phosphorylation, circumvents these subtype-specific differences and ubiquitously suppresses tumor growth, demonstrating the therapeutic utility of this approach in targeting deregulated MYC breast cancers.
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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.