ArticleNature2016
Tumour-cell-induced endothelial cell necroptosis via death receptor 6 promotes metastasis.
Article in Nature, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 339 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
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Who cites it
339 citing papers in PubMed, 560 citations in OpenAlex.
- E3 ubiquitin ligase-mediated necroptosis: regulatory mechanisms and therapeutic implication in cancer.Molecular biology reports · 2026Review
- Eggerthella lenta disrupts the gut vascular barrier to drive colorectal cancer liver metastasis.Cell discovery · 2026Article
- Discovery and Development of First-in-Class Cereblon-Recruiting RIPK1 Degraders.Journal of medicinal chemistry · 2026Article
- Review
- Tumoral extracellular vesicles and particles reprogram interstitial macrophages in the lung to promote vascular permeability and metastasis.Nature cancer · 2026Article
- Review
- Angiocrine factors in tumor microenvironment: bidirectional crosstalk, mechanistic insights, and therapeutic strategies.Journal of translational medicine · 2026Review
- Contemporary Endothelial Genome Editing Technologies: Towards Precision Genetic Medicine for Vascular Diseases.International journal of molecular sciences · 2026Review
- Regulated cell death programs shaping cancer therapy.Cellular oncology (Dordrecht, Netherlands) · 2026Review
- SPT6 maintains epidermal homeostasis by inhibiting an NF-κB-positive feedback loop to prevent excessive inflammation.Cellular & molecular immunology · 2026Article
- Programmed cell death in lung cancer: mechanisms, immune responses, and therapeutics.Apoptosis : an international journal on programmed cell death · 2026Review
- Discovery and Development of First-in-Class Cereblon-Recruiting RIPK1 Degraders.bioRxiv : the preprint server for biology · 2026Article
- Exosomal miR-92a-3p promotes pancreatic cancer cells' extravasation by inducing vascular permeability through inhibition of DAB2IP.Cell death & disease · 2026Article
- RIPK3 sequentially recruits MLKL and RIPK1 to induce PANoptosis and chemokine production.Cell death and differentiation · 2026Article
- Regulated necrosis at the crossroads of liver inflammation and cancer development.Nature reviews. Gastroenterology & hepatology · 2026Review
- Programmed cell death inhibitors: a new hope for cancer therapy?World journal of surgical oncology · 2026Review
- Breast cancer brain metastasis: mechanisms, emerging biomarkers, and therapeutic opportunities.American journal of cancer research · 2026Review
- Establishment of a Prognostic Necroptosis-Related lncRNA Signature in Ovarian Cancer.Combinatorial chemistry & high throughput screening · 2026Article
- Analysis of Necroptosis-Related Genes and Immune Cell Infiltration in Infantile Hemangioma.Endocrine, metabolic & immune disorders drug targets · 2026Article
- RIPK3 Protects Against Endothelial Activation and Vascular Permeability in a Mouse Model of Ischemia-Reperfusion Injury.Arteriosclerosis, thrombosis, and vascular biology · 2026Article
279 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
8 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Metastasis is the leading cause of cancer-related death in humans. It is a complex multistep process during which individual tumour cells spread primarily through the circulatory system to colonize distant organs. Once in the circulation, tumour cells remain vulnerable, and their metastatic potential largely depends on a rapid and efficient way to escape from the blood stream by passing the endothelial barrier. Evidence has been provided that tumour cell extravasation resembles leukocyte transendothelial migration. However, it remains unclear how tumour cells interact with endothelial cells during extravasation and how these processes are regulated on a molecular level. Here we show that human and murine tumour cells induce programmed necrosis (necroptosis) of endothelial cells, which promotes tumour cell extravasation and metastasis. Treatment of mice with the receptor-interacting serine/threonine-protein kinase 1 (RIPK1)-inhibitor necrostatin-1 or endothelial-cell-specific deletion of RIPK3 reduced tumour-cell-induced endothelial necroptosis, tumour cell extravasation and metastasis. In contrast, pharmacological caspase inhibition or endothelial-cell-specific loss of caspase-8 promoted these processes. We furthermore show in vitro and in vivo that tumour-cell-induced endothelial necroptosis leading to extravasation and metastasis requires amyloid precursor protein expressed by tumour cells and its receptor, death receptor 6 (DR6), on endothelial cells as the primary mediators of these effects. Our data identify a new mechanism underlying tumour cell extravasation and metastasis, and suggest endothelial DR6-mediated necroptotic signalling pathways as targets for anti-metastatic therapies.
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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.