ArticleCancer science2019
Delta-like 3 localizes to neuroendocrine cells and plays a pivotal role in gastrointestinal neuroendocrine malignancy.
Article in Cancer science, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed, 31 citations in OpenAlex.
- DLL3 expression in neuroendocrine carcinomas: a comparative analysis across tumor origins.Frontiers in endocrinology · 2026Article
- Crosstalk between GLTSCR1-deficient endothelial cells and tumour cells promotes colorectal cancer development by activating the Notch pathway.Cell death and differentiation · 2025Article
- Targeting DLL3: Innovative Strategies for Tumor Treatment.Pharmaceutics · 2025Review
- Harnessing delta-like ligand 3: bridging biomarker discovery to next-generation immunotherapies in refractory small cell lung cancer.Frontiers in immunology · 2025Review
- CAR-T therapy for neuroendocrine neoplasms: a review of molecular targets and clinical translation.Frontiers in immunology · 2025Review
- Delta-like ligand 3 (DLL3) landscape in pulmonary and extra-pulmonary neuroendocrine neoplasms.NPJ precision oncology · 2024Article
- HPN328, a Trispecific T Cell-Activating Protein Construct Targeting DLL3-Expressing Solid Tumors.Molecular cancer therapeutics · 2024Article
- Review
- Role of Bispecific Antibodies in Gastroenteropancreatic Neuroendocrine Neoplasms (GEP-NENs): Review of Literature.Clinical Medicine Insights. Oncology · 2024Review
- DLL3 Is a Prognostic and Potentially Predictive Biomarker for Immunotherapy Linked to PD/PD-L Axis and NOTCH1 in Pancreatic Cancer.Biomedicines · 2023Article
- Identification of DLL3-related genes affecting the prognosis of patients with colon adenocarcinoma.Frontiers in genetics · 2023Article
- Effects of mRNA expression of five Notch ligands on prognosis of gastric carcinoma.Scientific reports · 2022Article
- Glucose transporter‑1 inhibition overcomes imatinib resistance in gastrointestinal stromal tumor cells.Oncology reports · 2022Article
- Delta-like canonical Notch ligand 3 as a potential therapeutic target in malignancies: A brief overview.Cancer science · 2021Review
- DLL3 (delta-like protein 3) expression correlates with stromal desmoplasia and lymph node metastases in medullary thyroid carcinomas.Endocrine connections · 2021Article
- Prevalence of Delta-Like Protein 3 in a Consecutive Series of Surgically Resected Lung Neuroendocrine Neoplasms.Frontiers in oncology · 2021Article
- Management of Large Cell Neuroendocrine Carcinoma.Frontiers in oncology · 2021Review
- γ-H2AX as a potential indicator of radiosensitivity in colorectal cancer cells.Oncology letters · 2020Article
- Pleiotropic Role of Notch Signaling in Human Skin Diseases.International journal of molecular sciences · 2020Review
- The Role of DLLs in Cancer: A Novel Therapeutic Target.OncoTargets and therapy · 2020Review
Corrections and comments
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Authors and funding
13 authors at 1 institution in 1 country.
Funding
Abstract
Delta-like 3 (DLL3) is a member of the Delta/Serrate/Lag2 (DSL) group of Notch receptor ligands. Five DSL ligands are known in mammals, among which DLL3 has a unique structure. In the last few years, DLL3 has attracted attention as a novel molecular targeting gene in neuroendocrine carcinoma of the lung due to its high expression. However, the expression pattern and functions of DLL3 in the gastrointestinal tract and gastrointestinal neuroendocrine carcinoma remain unclear. In this study, we examined the expression and role of DLL3 in the gastrointestinal tract, as well as in gastrointestinal neuroendocrine carcinoma. Immunohistochemical staining of the human normal gastrointestinal tract revealed that DLL3 localized in neuroendocrine cells. DLL3 showed intense staining in chromogranin A-positive gastric cancer specimens. Real-time quantitative RT-PCR and western blotting analyses showed considerable upregulation of DLL3 in gastrointestinal neuroendocrine carcinoma cell lines. Immuno-electron microscopy demonstrated abundant expression of DLL3 in neurosecretory granules in these cells. Furthermore, gene silencing of DLL3 caused significant growth inhibition through the induction of intrinsic apoptosis. Our findings suggest that DLL3 is expressed in neuroendocrine cells of the gastrointestinal tract and that it has a pivotal role in gastrointestinal neuroendocrine carcinoma cells. Based on these findings, further investigations are required to achieve a breakthrough in developing therapeutic strategies for gastrointestinal neuroendocrine carcinoma.
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Registered trials
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