ArticleOncotarget2014
Endothelial Delta-like 4 (DLL4) promotes renal cell carcinoma hematogenous metastasis.
Article in Oncotarget, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers, 1 of them a synthesis that pooled it.
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Who cites it
26 citing papers in PubMed, 1 synthesis or guideline pooled it, 36 citations in OpenAlex.
- Signaling pathway mechanisms in pancreatic ductal adenocarcinoma tumor microenvironment and emerging targeting strategies for improved prognosis.Oncology reviews · 2026Pooled it
- IFNγ-dependent metabolic reprogramming restrains an immature, pro-metastatic lymphatic state in melanoma.Cancer cell · 2026Article
- The Prediction of DLL4 as a Prognostic Biomarker in Patients with Gastric Cancer Using Anti-DLL4 Nanobody.Journal of gastrointestinal cancer · 2024Article
- Cellular crosstalk of mesangial cells and tubular epithelial cells in diabetic kidney disease.Cell communication and signaling : CCS · 2023Review
- Biomarkers in renal cell carcinoma and their targeted therapies: a review.Exploration of targeted anti-tumor therapy · 2023Review
- The role of calcium oscillations in the phenotype selection in endothelial cells.Scientific reports · 2021Article
- Control of Tumor Progression by Angiocrine Factors.Cancers · 2021Review
- Article
- CD146 as a Prognostic-Related Biomarker in ccRCC Correlating With Immune Infiltrates.Frontiers in oncology · 2021Article
- FGL1 as a Novel Mediator and Biomarker of Malignant Progression in Clear Cell Renal Cell Carcinoma.Frontiers in oncology · 2021Article
- Review
- Androgen receptor modulates metastatic routes of VHL wild-type clear cell renal cell carcinoma in an oxygen-dependent manner.Oncogene · 2020Article
- Tumor-educated B cells promote renal cancer metastasis via inducing the IL-1β/HIF-2α/Notch1 signals.Cell death & disease · 2020Article
- Inhibition of Delta-like Ligand 4 enhances the radiosensitivity and inhibits migration in cervical cancer via the reversion of epithelial-mesenchymal transition.Cancer cell international · 2020Article
- The Role of DLLs in Cancer: A Novel Therapeutic Target.OncoTargets and therapy · 2020Review
- Metastasis is impaired by endothelial-specific Dll4 loss-of-function through inhibition of epithelial-to-mesenchymal transition and reduction of cancer stem cells and circulating tumor cells.Clinical & experimental metastasis · 2019Article
- Study of Cathepsin B inhibition in VEGFR TKI treated human renal cell carcinoma xenografts.Oncogenesis · 2019Article
- A 44-gene set constructed for predicting the prognosis of clear cell renal cell carcinoma.International journal of molecular medicine · 2018Article
- UpregulatedOncoTargets and therapy · 2018Article
- Androgen receptor increases hematogenous metastasis yet decreases lymphatic metastasis of renal cell carcinoma.Nature communications · 2017Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
11 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The Notch ligand Delta-like 4 (DLL4) plays an important role in tumor angiogenesis, which is required for tumor invasion and metastasis. Here we showed that DLL4 was elevated in endothelium and Notch signaling was activated in renal cell carcinoma (RCC). Exogenous DLL4 induced RCC cell migration and invasion by activating intercellular Notch signaling. Importantly, the DLL4/Notch/Hey1/MMP9 cascades connecting the endothelium to the cancer cells in metastasis were identified. Knockdown of Hey1 decreased expression of MMP9 and attenuated tumor invasion. The clinical investigation on 120 cases of RCC specimens indicated that expressions of Hey1 and MMP9 correlated with DLL4 density. Moreover, univariate and multivariate analyses showed that tumor hematogenous metastasis not only was depended on microvessel density but was also associated with tumor size and DLL4 density. During 4-year surveillance, high-level of DLL4 density was associated with a higher probability of developing metastasis and being sensitive to target therapies. Our data suggest that RCC progression is caused in part by activated DLL4/Notch signaling, interaction of endothelium and cells, which can be therapeutically targeted.
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