ArticleCancer science2020
TNF-α enhances TGF-β-induced endothelial-to-mesenchymal transition via TGF-β signal augmentation.
Article in Cancer science, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 98 papers, 1 of them a synthesis that pooled it.
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The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
98 citing papers in PubMed, 1 synthesis or guideline pooled it, 155 citations in OpenAlex.
- What is the Impact of Endothelial-to-Mesenchymal Transition in Solid Tumours: A Qualitative Systematic Review and Quantitative Meta-Analysis.International journal of biological sciences · 2025Pooled it
- Macrophage immunometabolic reprogramming in inflammatory repair failure in osteonecrosis of the femoral head.Journal of orthopaedic translation · 2026Review
- Beyond EMT: Mesenchymal drift as an emerging driver of stromal-immune reprogramming in prostate cancer.iScience · 2026Review
- Single-cell transcriptomics highlights macrophage-driven regulation of EndMT and repair in injured muscle.Communications biology · 2026Article
- EndMT in vascular cognitive impairment and dementia: mechanisms, evidence gaps, and therapeutic opportunities.Molecular medicine (Cambridge, Mass.) · 2026Review
- TGF-β and TNF-α Signaling Crosstalk in Human Coronary Artery Cells.International journal of molecular sciences · 2026Article
- Atherosclerotic Fibrous Plaques in Women Present ECM Remodeling Linked to TGF-β.Circulation research · 2026Article
- Inflammatory milieu and role of epigenetic modifications in high-grade serous ovarian cancer.Clinical epigenetics · 2026Review
- Role of tumor microenvironment in regulator of tumor progression and immunotherapy.Discover oncology · 2026Review
- WuYeLuGen Granule Attenuates Bleomycin-Induced Pulmonary Fibrosis in Rats by Inhibiting the TGF-β1/Smad Signaling Pathway and Epithelial-Mesenchymal Transition.Canadian respiratory journal · 2026Article
- Intracavernous Injection of Mechanically Extracted Stromal Vascular Fragments Suppresses Endothelial-Mesenchymal Transformation to Mitigate Erectile Dysfunction in Hypertensive Rats.Stem cells international · 2026Article
- TNFα and Endothelial IL-1 Receptor Signaling Drive Peritubular Capillary Regression and Fibrosis in Obstructive Kidney Injury.bioRxiv : the preprint server for biology · 2025Article
- Endothelial-to-Mesenchymal Transition in Health and Disease: Molecular Insights and Therapeutic Implications.International journal of molecular sciences · 2025Review
- Brain metastasis from non-small cell lung cancer: crosstalk between cancer cells and tumor microenvironment components.Experimental & molecular medicine · 2025Review
- Citrullinated and Malondialdehyde-Acetaldehyde-Modified Fibrinogen Activates Macrophages and Promotes Coronary Endothelial Cell Inflammation.Current issues in molecular biology · 2025Article
- Reconceptualizing Endothelial-to-mesenchymal transition in atherosclerosis: Signaling pathways and prospective targeting strategies.Journal of advanced research · 2025Review
- Endothelial-to-mesenchymal transition in the central nervous system: A potential therapeutic target to combat age-related vascular fragility.The Journal of pharmacology and experimental therapeutics · 2025Review
- Lipid raft proteomics identify endothelial myosin-9 (MYH9) as a regulator of low-density lipoprotein transcytosis and atherosclerosis.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Endothelial-Mesenchymal Transition in Tumor Microenvironment Promotes Neuroendocrine Differentiation of Prostate Cancer.Cancer science · 2025Article
- Article
38 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
11 authors at 4 institutions in 1 country.
Funding
Abstract
The tumor microenvironment (TME) consists of various components including cancer cells, tumor vessels, cancer-associated fibroblasts (CAFs), and inflammatory cells. These components interact with each other via various cytokines, which often induce tumor progression. Thus, a greater understanding of TME networks is crucial for the development of novel cancer therapies. Many cancer types express high levels of TGF-β, which induces endothelial-to-mesenchymal transition (EndMT), leading to formation of CAFs. Although we previously reported that CAFs derived from EndMT promoted tumor formation, the molecular mechanisms underlying these interactions remain to be elucidated. Furthermore, tumor-infiltrating inflammatory cells secrete various cytokines, including TNF-α. However, the role of TNF-α in TGF-β-induced EndMT has not been fully elucidated. Therefore, this study examined the effect of TNF-α on TGF-β-induced EndMT in human endothelial cells (ECs). Various types of human ECs underwent EndMT in response to TGF-β and TNF-α, which was accompanied by increased and decreased expression of mesenchymal cell and EC markers, respectively. In addition, treatment of ECs with TGF-β and TNF-α exhibited sustained activation of Smad2/3 signals, which was presumably induced by elevated expression of TGF-β type I receptor, TGF-β2, activin A, and integrin αv, suggesting that TNF-α enhanced TGF-β-induced EndMT by augmenting TGF-β family signals. Furthermore, oral squamous cell carcinoma-derived cells underwent epithelial-to-mesenchymal transition (EMT) in response to humoral factors produced by TGF-β and TNF-α-cultured ECs. This EndMT-driven EMT was blocked by inhibiting the action of TGF-βs. Collectively, our findings suggest that TNF-α enhances TGF-β-dependent EndMT, which contributes to tumor progression.
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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.