ArticleNature communications2020
Primary tumors release ITGBL1-rich extracellular vesicles to promote distal metastatic tumor growth through fibroblast-niche formation.
Article in Nature communications, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 183 papers, 3 of them syntheses that pooled it.
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Who cites it
183 citing papers in PubMed, 3 syntheses or guidelines pooled it, 281 citations in OpenAlex.
- Global hotspots and trends in pre-metastatic niche research: a bibliometric analysis(2005-2024).Frontiers in immunology · 2025Pooled it
- Pooled it
- Tumour-derived exosomes in liver metastasis: A Pandora's box.Cell proliferation · 2023Pooled it
- Dental pulp cell-derived conditioned culture media promotes periodontal repair through immunomodulation and bone regeneration.Regenerative therapy · 2026Article
- HDCA suppresses exosomal lncRNA MSTRG171708 release to inhibit Treg-mediated immunometabolism in hepatocellular carcinoma.Molecular biomedicine · 2026Article
- The lethal symbiont: exploring the pathophysiology of cancer.Physiological reviews · 2026Review
- Single-cell transcriptomics profiling elucidates RBP-driven metastatic signaling pathways in ERiScience · 2026Article
- CA9 targets ITGB1 to accelerate the progression of colorectal cancer by promoting the neutrophil extracellular traps formation.Journal of translational medicine · 2026Article
- Exosomal integrin αvβ3 derived from colorectal cancer promotes the liver pre-metastatic niche formation by inducing cancer-associated fibroblasts activation.Clinical and experimental medicine · 2026Article
- HSP90AB1-Mediated Ubiquitin-Proteasome Degradation of ITGBL1 Promotes Osteosarcoma Progression by Inhibiting Endoplasmic Reticulum Stress-Induced Autophagy.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Heterogeneity and plasticity of cancer-associated fibroblasts.Nature cancer · 2026Review
- The pre-metastatic niche: mechanisms, heterogeneity, and therapeutic opportunities.Molecular cancer · 2026Review
- TRIM27-controlled endothelium-derived exosomes play a central role in podocyte injury in diabetic kidney disease.Cell death discovery · 2026Article
- Contribution of tumor-derived extracellular vesicles in the establishment of the pre-metastatic niche: lessons learned from past experimentations and future directions.Clinical & experimental metastasis · 2026Review
- Base barrier cells provide compartmentalization of choroid plexus, brain and CSF.Nature neuroscience · 2026Article
- Cancer-associated fibroblasts as a critical driver in tumor metastasis: The mechanisms and future perspectives.iScience · 2026Review
- LOX From Salivary Adenoid Cystic Carcinoma-Associated Fibroblast Promotes Fibrosis in the Pulmonary Pre-metastatic Niche.International dental journal · 2026Article
- Annexin A2-dependent extracellular vesicle proteome modulates pre-metastatic stromal fibroblast behavior in triple-negative breast cancer.Cell communication and signaling : CCS · 2026Article
- Extracellular vesicle-derived miRNA-182-5p educates macrophages towards an immunosuppressive phenotype in pancreatic cancer.Signal transduction and targeted therapy · 2026Article
- PRL-3 up-regulates exosomal ITGαvβ5 expression to promote liver pre-metastatic niche formation and colon cancer liver metastasis.Experimental hematology & oncology · 2026Article
123 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
20 authors at 4 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Tumor metastasis is a hallmark of cancer. Metastatic cancer cells often reside in distal tissues and organs in their dormant state. Mechanisms underlying the pre-metastatic niche formation are poorly understood. Here we show that in a colorectal cancer (CRC) model, primary tumors release integrin beta-like 1 (ITGBL1)-rich extracellular vesicles (EVs) to the circulation to activate resident fibroblasts in remote organs. The activated fibroblasts induce the pre-metastatic niche formation and promote metastatic cancer growth by secreting pro-inflammatory cytokine, such as IL-6 and IL-8. Mechanistically, the primary CRC-derived ITGBL1-enriched EVs stimulate the TNFAIP3-mediated NF-κB signaling pathway to activate fibroblasts. Consequently, the activated fibroblasts produce high levels of pro-inflammatory cytokines to promote metastatic cancer growth. These findings uncover a tumor-stromal interaction in the metastatic tumor microenvironment and an intimate signaling communication between primary tumors and metastases through the ITGBL1-loaded EVs. Targeting the EVs-ITGBL1-CAFs-TNFAIP3-NF-κB signaling axis provides an attractive approach for treating metastatic diseases.
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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.