ArticleCancer medicine2017
DLL4 overexpression increases gastric cancer stem/progenitor cell self-renewal ability and correlates with poor clinical outcome via Notch-1 signaling pathway activation.
Article in Cancer medicine, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers, 1 of them a synthesis that pooled it.
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Who cites it
27 citing papers in PubMed, 1 synthesis or guideline pooled it, 35 citations in OpenAlex.
- Nestin Expression and the Survival of Patients With Digestive Tract Cancers: A Systematic Review and Meta-Analysis.The Turkish journal of gastroenterology : the official journal of Turkish Society of Gastroenterology · 2023Pooled it
- DLL4-targeted CAR-T therapy sensitizes neoadjuvant chemotherapy via eliminating cancer stem cells and reshaping immune microenvironment in HER2Journal for immunotherapy of cancer · 2024Article
- THBS2 promotes gastric cancer progression and stemness via the Notch signaling pathway.American journal of cancer research · 2024Article
- Exploring the dynamic interplay between cancer stem cells and the tumor microenvironment: implications for novel therapeutic strategies.Journal of translational medicine · 2023Review
- Tumor cell stemness in gastrointestinal cancer: regulation and targeted therapy.Frontiers in molecular biosciences · 2023Review
- Review
- Effects of mRNA expression of five Notch ligands on prognosis of gastric carcinoma.Scientific reports · 2022Article
- The Prognostic Role and Significance of Dll4 and Toll-like Receptors in Cancer Development.Cancers · 2022Review
- Atractylenolide III Attenuates Angiogenesis in Gastric Precancerous Lesions Through the Downregulation of Delta-Like Ligand 4.Frontiers in pharmacology · 2022Article
- Cancer Stem Cells: From an Insight into the Basics to Recent Advances and Therapeutic Targeting.Stem cells international · 2022Review
- Targeting Notch to Maximize Chemotherapeutic Benefits: Rationale, Advanced Strategies, and Future Perspectives.Cancers · 2021Review
- Linc00641 promotes the progression of gastric carcinoma by modulating the miR-429/Notch-1 axis.Aging · 2021Article
- Suppression of human colon tumor by EERAC through regulating Notch/DLL4/Hes pathway inhibiting angiogenesisJournal of Cancer · 2021Article
- Cancer stem cells: a major culprit of intra-tumor heterogeneity.American journal of cancer research · 2021Review
- Synergistic antitumor activity of a DLL4/VEGF bispecific therapeutic antibody in combination with irinotecan in gastric cancer.BMB reports · 2020Article
- Targeting cancer stem cell pathways for cancer therapy.Signal transduction and targeted therapy · 2020Review
- Notch1 and PI3K/Akt signaling blockers DAPT and LY294002 coordinately inhibit metastasis of gastric cancer through mutual enhancement.Cancer chemotherapy and pharmacology · 2020Article
- The Role of DLLs in Cancer: A Novel Therapeutic Target.OncoTargets and therapy · 2020Review
- Identification of Prognostic Model and Biomarkers for Cancer Stem Cell Characteristics in Glioblastoma by Network Analysis of Multi-Omics Data and Stemness Indices.Frontiers in cell and developmental biology · 2020Article
- Peritoneal Metastatic Cancer Stem Cells of Gastric Cancer with Partial Mesenchymal-Epithelial Transition and Enhanced Invasiveness in an Intraperitoneal Transplantation Model.Gastroenterology research and practice · 2020Article
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Gastric cancer is one of the most common malignant diseases, and poses a serious threat to the quality of human life. Gastric cancer stem/progenitor cells (GCSPCs) have critical effects on tumor formation, affecting specific features of self-renewal and differentiation and playing a critical role in metastasis. The Notch-1 pathway is crucially important to GCSPCs and is regulated by DLL4. In this study, DLL4 and Nestin levels were measured in 383 gastric cancer tissue samples by immunohistochemistry, and the clinico-pathological features of patients assessed. After DLL4 silencing in selected gastric cancer cell lines, the expression of GCSPC markers and colony formation ability were analyzed and the self-renewal and differentiation capacities of the cells were evaluated. The relationship between DLL4 levels and Notch-1 signaling pathway effector amounts was assessed via Western blotting and immunofluorescence. Finally, the tumor formation ability of the gastric cancer cells was evaluated with different levels of DLL4 and multiple cell densities in vivo. Our results indicate that DLL4 expression is associated with TNM stage and cancer metastasis, with high amounts of DLL4 leading to poor outcome. DLL4 silencing inhibited the self-renewal ability of GCSPCs and increased their multidifferentiation capacity, resulting in reduced GCSPC ratios. DLL4 knockdown also blocked the Notch-1 pathway, weakening invasion ability and resistance to 5-FU chemotherapy. In vivo, DLL4 silencing inhibited the tumor formation ability of GCSPCs. In conclusion, DLL4 affects GCSPC stemness, altering their pathological behavior. DLL4 silencing inhibits GCSPC metastatic potential both in vitro and in vivo by impeding Notch-1 signaling pathway activation, indicating that DLL4 may be a new potential therapeutic target.
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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.