ArticleOncogene2012
Neutralization of the γ-secretase activity by monoclonal antibody against extracellular domain of nicastrin.
Article in Oncogene, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers.
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
33 citing papers in PubMed, 66 citations in OpenAlex.
- Expression of nicastrin, NICD1, and Hes1 in NCSTN knockout mice: implications for hidradenitis suppurativa, Alzheimer's, and liver cancer.European journal of medical research · 2024Article
- Role of Notch2 pathway in mature B cell malignancies.Frontiers in oncology · 2022Review
- Nicastrin-Like, a Novel Transmembrane Protein fromMicroorganisms · 2021Article
- [The role and research progress of NOTCH1 in T-cell acute lymphoblastic leukemia].Zhonghua xue ye xue za zhi = Zhonghua xueyexue zazhi · 2021Article
- Notch Signalling in Breast Development and Cancer.Frontiers in cell and developmental biology · 2021Review
- Cancer Stem Cells,Cells · 2020Review
- Specific Targeting of Notch Ligand-Receptor Interactions to Modulate Immune Responses: A Review of Clinical and Preclinical Findings.Frontiers in immunology · 2020Review
- Therapeutic Targeting of Notch Signaling Pathway in Hematological Malignancies.Mediterranean journal of hematology and infectious diseases · 2019Review
- Review
- High-efficient production and biophysical characterisation of nicastrin and its interaction with APPC100.Scientific reports · 2017Article
- The genetics and molecular biology of T-ALL.Blood · 2017Review
- Notch signaling: its roles and therapeutic potential in hematological malignancies.Oncotarget · 2016Review
- Targeting Notch to overcome radiation resistance.Oncotarget · 2016Review
- Targeting of proangiogenic signalling pathways in chronic inflammation.Nature reviews. Rheumatology · 2016Review
- Functional Variants in Notch Pathway Genes NCOR2, NCSTN, and MAML2 Predict Survival of Patients with Cutaneous Melanoma.Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology · 2015Article
- Cooperative roles of hydrophilic loop 1 and the C-terminus of presenilin 1 in the substrate-gating mechanism of γ-secretase.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2015Article
- A synthetic antibody fragment targeting nicastrin affects assembly and trafficking of γ-secretase.The Journal of biological chemistry · 2014Article
- Targeting Notch Signaling in Colorectal Cancer.Current colorectal cancer reports · 2014Article
- Anti-nicastrin monoclonal antibodies elicit pleiotropic anti-tumour pharmacological effects in invasive breast cancer cells.Breast cancer research and treatment · 2014Article
- Nicastrin and Notch4 drive endocrine therapy resistance and epithelial to mesenchymal transition in MCF7 breast cancer cells.Breast cancer research : BCR · 2014Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
16 authors at 6 institutions in 2 countries.
Funding
Abstract
Several lines of evidence suggest that aberrant Notch signaling contributes to the development of several types of cancer. Activation of Notch receptor is executed through intramembrane proteolysis by γ-secretase, which is a multimeric membrane-embedded protease comprised of presenilin, nicastrin (NCT), anterior pharynx defective 1 and PEN-2. In this study, we report the neutralization of the γ-secretase activity by a novel monoclonal antibody A5226A against the extracellular domain of NCT, generated by using a recombinant budded baculovirus as an immunogen. This antibody recognized fully glycosylated mature NCT in the active γ-secretase complex on the cell surface, and inhibited the γ-secretase activity by competing with the substrate binding in vitro. Moreover, A5226A abolished the γ-secretase activity-dependent growth of cancer cells in a xenograft model. Our data provide compelling evidence that NCT is a molecular target for the mechanism-based inhibition of γ-secretase, and that targeting NCT might be a novel therapeutic strategy against cancer caused by aberrant γ-secretase activity and Notch signaling.
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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.