ArticleOncotarget2015
Lateral inhibition of Notch signaling in neoplastic cells.
Article in Oncotarget, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed.
- Notch and Hedgehog Signaling Unveiled: Crosstalk, Roles, and Breakthroughs in Cancer Stem Cell Research.Life (Basel, Switzerland) · 2025Review
- NOTCH pathway inactivation reprograms stem-like oral cancer cells to JAK-STAT dependent state and provides the opportunity of synthetic lethality.Translational oncology · 2023Article
- Immunotherapy and the Combination with Targeted Therapies for Advanced Hepatocellular Carcinoma.Cancers · 2023Review
- DLL3 regulates Notch signaling in small cell lung cancer.iScience · 2022Article
- Notch1 Deficiency Induces Tumor Cell Accumulation Inside the Bronchiolar Lumen and Increases TAZ Expression in an AutochthonousPathology oncology research : POR · 2021Article
- MAPK and Notch-Mediated Effects of Meso-Xanthin F199 Compounds on Proliferative Activity and Apoptosis of Human Melanocytes in Three-Dimensional Culture.BioMed research international · 2021Article
- Review
- Cancer Stem Cells,Cells · 2020Review
- IL-4-dependent Jagged1 expression/processing is associated with survival of chronic lymphocytic leukemia cells but not with Notch activation.Cell death & disease · 2018Article
- Notch signaling promotes a HIF2α-driven hypoxic response in multiple tumor cell types.Oncogene · 2018Article
- NOTCH1 Aberrations in Chronic Lymphocytic Leukemia.Frontiers in oncology · 2018Review
- Targeting Notch3 in Hepatocellular Carcinoma: Molecular Mechanisms and Therapeutic Perspectives.International journal of molecular sciences · 2016Review
- Targeting Notch signaling as a novel therapy for retinoblastoma.Oncotarget · 2016Article
- Fine-Tuning of the Kaposi's Sarcoma-Associated Herpesvirus Life Cycle in Neighboring Cells through the RTA-JAG1-Notch Pathway.PLoS pathogens · 2016Article
Corrections and comments
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Authors and funding
7 authors.
Funding
Abstract
During normal development, heterogeneous expression of Notch ligands can result in pathway suppression in the signal-sending cell, a process known as lateral inhibition. It is unclear if an analogous phenomenon occurs in malignant cells. We observed significant induction of Notch ligands in glioblastoma neurospheres and pancreatic carcinoma cells cultured in low oxygen, suggesting that this phenomenon could occur around hypoxic regions. To model lateral inhibition in these tumors, the ligand Jagged1 was overexpressed in glioblastoma and pancreatic carcinoma cells, resulting in overall induction of pathway targets. However, when ligand high and ligand low cells from a single line were co-cultured and then separated, we noted suppression of Notch pathway targets in the former and induction in the latter, suggesting that neoplastic lateral inhibition can occur. We also found that repression of Notch pathway targets in signal-sending cells may occur through the activity of a Notch ligand intracellular domain, which translocates into the nucleus. Understanding how this neoplastic lateral inhibition process functions in cancer cells may be important in targeting ligand driven Notch signaling in solid tumors.
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