ArticleOncogene2011
The lymphovascular embolus of inflammatory breast cancer exhibits a Notch 3 addiction.
Article in Oncogene, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.
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Who cites it
29 citing papers in PubMed, 50 citations in OpenAlex.
- E-Cadherin Regulates HIF1-α In Vitro in Induced 3D Spheroid Models of Human Breast Cancer Through Both mTOR and Notch1 Signaling.Biomedicines · 2025Article
- True cancer stem cells exhibit relative degrees of dormancy and genomic stability.Neoplasia (New York, N.Y.) · 2025Article
- KK-LC-1 as a therapeutic target to eliminate ALDHNature communications · 2023Article
- Geometric tumor embolic budding characterizes inflammatory breast cancer.Breast cancer research and treatment · 2023Article
- Comparative transcriptional analyses of preclinical models and patient samples reveal MYC and RELA driven expression patterns that define the molecular landscape of IBC.NPJ breast cancer · 2022Article
- Three-Dimensional Culture Systems for Dissecting Notch Signalling in Health and Disease.International journal of molecular sciences · 2021Review
- The Role of Notch3 Signaling in Cancer Stemness and Chemoresistance: Molecular Mechanisms and Targeting Strategies.Frontiers in molecular biosciences · 2021Review
- A Molecular Test for Quantifying Functional Notch Signaling Pathway Activity in Human Cancer.Cancers · 2020Article
- Epigenetics in Inflammatory Breast Cancer: Biological Features and Therapeutic Perspectives.Cells · 2020Review
- NOTCH and DNA repair pathways are more frequently targeted by genomic alterations in inflammatory than in non-inflammatory breast cancers.Molecular oncology · 2020Article
- Identification of Potential Key Genes and Pathways for Inflammatory Breast Cancer Based on GEO and TCGA Databases.OncoTargets and therapy · 2020Article
- Biomarkers for Inflammatory Breast Cancer: Diagnostic and Therapeutic Utility.Breast cancer (Dove Medical Press) · 2020Review
- Inflammatory breast cancer: Activation of the aryl hydrocarbon receptor and its target CYP1B1 correlates closely with Wnt5a/b-β-catenin signalling, the stem cell phenotype and disease progression.Journal of advanced research · 2019Article
- Toward understanding cancer stem cell heterogeneity in the tumor microenvironment.Proceedings of the National Academy of Sciences of the United States of America · 2019Article
- Inflammatory breast cancer biology: the tumour microenvironment is key.Nature reviews. Cancer · 2018Review
- The Role ofThe oncologist · 2018Review
- MAD2L2 inhibits colorectal cancer growth by promoting NCOA3 ubiquitination and degradation.Molecular oncology · 2018Article
- Inflammatory breast cancer: a model for investigating cluster-based dissemination.NPJ breast cancer · 2017Article
- Correlation ofJournal of Cancer · 2017Article
- New targeted therapies for breast cancer: A focus on tumor microenvironmental signals and chemoresistant breast cancers.World journal of clinical cases · 2014Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
8 authors at 2 institutions in 1 country.
Funding
Abstract
Inflammatory breast carcinoma (IBC) is characterized by exaggerated lymphovascular invasion (LVI), recapitulated in our human xenograft, MARY-X. This model exhibited lymphovascular emboli in vivo and corresponding spheroids in vitro. Owing to the morphological and gene profile resemblance of these spheroids to embryonal blastocysts, we wondered whether they might exhibit embryonic stem cell signaling. Specifically we investigated Notch and observed selective Notch 3 activation by expression profiling, reverse transcriptase- and real-time PCR, western blot and immunofluorescence in vitro, and immunohistochemistry in vivo. Notch 3 intracellular domain (N3icd) and six target genes, HES-5, HEY-1, c-Myc, Deltex-1, NRARP and PBX1, markedly increased in MARY-X. In addition, a significant percentage of MARY-X cells expressed aldehyde dehydrogenase (ALDH), a stem cell marker. Only the ALDH(+) cells were capable of secondary spheroidgenesis, tumorigenicity and self-renewal. Inhibiting Notch 3 activation in vitro with γ-secretase inhibitors (GSIs) or small interfering RNA resulted in a downregulation of Notch target genes, including CD133, and an induction of caspase 3-mediated apoptosis. Transfection of N3icd but not Notch 1 intracellular domain into normal human mammary epithelial cells resulted in increased expression of Notch target genes and induction of spheroidgenesis. GSI in vivo resulted in inhibitory but diffusion-limited effects on Notch 3 signaling, resulting in xenograft growth reduction. The lymphovascular emboli of human IBC exhibited dual N3icd and ALDH1 immunoreactivities independently of molecular subtype. This Notch 3 addiction of lymphovascular emboli might be exploited in future therapeutic strategies.
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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.