ArticleThe Journal of clinical investigation2020
Inactivation of endothelial ZEB1 impedes tumor progression and sensitizes tumors to conventional therapies.
Article in The Journal of clinical investigation, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers.
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Who cites it
32 citing papers in PubMed, 64 citations in OpenAlex.
- Role of ZEB1 in angiogenesis and therapeutic potential (Review).International journal of molecular medicine · 2026Review
- P4HA1⁺ collagen-modifying fibroblasts are associated with pro-tumor niches and therapeutic vulnerabilities in colorectal cancer.Journal of translational medicine · 2026Article
- ZEB1 Modifies VE-Cadherin Signaling in Lymphatic Endothelial Cells.Microcirculation (New York, N.Y. : 1994) · 2026Article
- Dual function of DOT1L suppresses tumor cell-intrinsic immunogenicity in hepatocellular carcinoma.Oncogene · 2026Article
- Zeb1 Facilitates Nitrogen Mustard-Induced Corneal Epithelial Wound Healing by Maintaining Epithelial Renewability.Investigative ophthalmology & visual science · 2025Article
- Comprehensive treatment of intermediate and advanced primary hepatocellular carcinoma based on transcatheter arterial chemoembolization (Review).Oncology letters · 2025Review
- GLI2 inhibits cisplatin sensitivity in gastric cancer through DEC1/ZEB1 mediated EMT.Cell death & disease · 2025Article
- SB218078 inhibits angiogenesis and epithelial-mesenchymal transition in breast cancer.Frontiers in pharmacology · 2025Article
- The perspective of ceRNA regulation of circadian rhythm on choroidal neovascularization.Scientific reports · 2024Article
- Galunisertib promotes bevacizumab-induced vascular normalization in nasopharyngeal carcinoma: Multi-parameter MRI evaluation.Molecular therapy. Oncology · 2024Article
- An 18-gene signature of recurrence-associated endothelial cells predicts tumor progression and castration resistance in prostate cancer.British journal of cancer · 2024Article
- Mouse Models to Evaluate the Functional Role of the Tumor Microenvironment in Cancer Progression and Therapy Responses.Cold Spring Harbor perspectives in medicine · 2024Review
- Corneal injury repair and the potential involvement of ZEB1.Eye and vision (London, England) · 2024Review
- CD40 is expressed in the subsets of endothelial cells undergoing partial endothelial-mesenchymal transition in tumor microenvironment.Cancer science · 2024Article
- TGF-βR2 signaling coordinates pulmonary vascular repair after viral injury in mice and human tissue.Science translational medicine · 2024Article
- Hypoxia-induced ZEB1 promotes cervical cancer immune evasion by strengthening the CD47-SIRPα axis.Cell communication and signaling : CCS · 2024Article
- Lymphangiogenesis in gastric cancer: function and mechanism.European journal of medical research · 2023Review
- Analysis of Sonazoid contrast-enhanced ultrasound for predicting the risk of microvascular invasion in hepatocellular carcinoma: a prospective multicenter study.European radiology · 2023Article
- JP1 normalizes tumor vasculature to suppress metastasis and facilitate drug delivery by inhibiting IL-8.JCI insight · 2023Article
- Anticancer Activity of Mannose-Specific Lectin, BPL2, from Marine Green AlgaMarine drugs · 2022Article
Corrections and comments
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Authors and funding
12 authors at 3 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Current antiangiogenic therapy is limited by its cytostatic property, scarce drug delivery to the tumor, and side toxicity. To address these limitations, we unveiled the role of ZEB1, a tumor endothelium-enriched zinc-finger transcription factor, during tumor progression. We discovered that the patients who had lung adenocarcinomas with high ZEB1 expression in tumor endothelium had increased prevalence of metastases and markedly reduced overall survival after the diagnosis of lung cancer. Endothelial ZEB1 deletion in tumor-bearing mice diminished tumor angiogenesis while eliciting persistent tumor vascular normalization by epigenetically repressing TGF-β signaling. This consequently led to improved blood and oxygen perfusion, enhanced chemotherapy delivery and immune effector cell infiltration, and reduced tumor growth and metastasis. Moreover, targeting vascular ZEB1 remarkably potentiated the anticancer activity of nontoxic low-dose cisplatin. Treatment with low-dose anti-programmed cell death protein 1 (anti-PD-1) antibody elicited tumor regression and markedly extended survival in ZEB1-deleted mice, conferring long-term protective anticancer immunity. Collectively, we demonstrated that inactivation of endothelial ZEB1 may offer alternative opportunities for cancer therapy with minimal side effects. Targeting endothelium-derived ZEB1 in combination with conventional chemotherapy or immune checkpoint blockade therapy may yield a potent and superior anticancer effect.
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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.