ArticleThe Journal of clinical investigation2022
Tumor-specific interendothelial adhesion mediated by FLRT2 facilitates cancer aggressiveness.
Article in The Journal of clinical investigation, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed, 27 citations in OpenAlex.
- ITPG: an immune-related transcriptomic predictive model for gastric cancer prognosis.Translational cancer research · 2026Article
- Investigating the impact of MCTP2 on immune suppression and drug resistance in glioblastoma.Functional & integrative genomics · 2025Article
- Endothelial c-Maf prevents MASLD-like liver fibrosis by regulating chromatin accessibility to suppress pathogenic microvascular cell subsets.JHEP reports : innovation in hepatology · 2025Article
- Identification of a subpopulation of highly adherent endothelial cells for seeding synthetic vascular grafts.The Journal of thoracic and cardiovascular surgery · 2025Article
- A review of the carcinogenic potential of human papillomavirus (HPV) in urological cancers.Virology journal · 2025Review
- Irradiation-responsive PRDM10-DT modulates the angiogenic response in human NSCLC cells in an SP1-dependent manner via the miR-663a/TGF-β1 axis.Journal of translational medicine · 2025Article
- HPV-Associated Gene Signatures in Bladder Cancer: A Comprehensive Prognostic Model and its Implications in Immunotherapy.International journal of medical sciences · 2025Article
- Regulatory T cells crosstalk with tumor cells and endothelium through lymphotoxin signaling.Nature communications · 2024Article
- Vascular FLRT2 regulates venous-mediated angiogenic expansion and CNS barriergenesis.Nature communications · 2024Article
- Mechanisms of ferroptosis and targeted therapeutic approaches in urological malignancies.Cell death discovery · 2024Review
- The NEDD4/FLRT2 axis regulates NSCLC cell stemness.Frontiers in pharmacology · 2024Article
- Rejection of inappropriate synaptic partners in mouse retina mediated by transcellular FLRT2-UNC5 signaling.Developmental cell · 2023Article
- A Novel Molecular Analysis Approach in Colorectal Cancer Suggests New Treatment Opportunities.Cancers · 2023Article
- Vascular and Neuronal Network Formation Regulated by Growth Factors and Guidance Cues.Life (Basel, Switzerland) · 2023Review
- Effective oxygen metabolism-based prognostic signature for colorectal cancer.Frontiers in oncology · 2023Article
- Single-cell analysis of multiple cancer types reveals differences in endothelial cells between tumors and normal tissues.Computational and structural biotechnology journal · 2023Article
- Identification ofFrontiers in oncology · 2023Article
- Anti-PD-L1 therapy altered inflammation but not survival in a lethal murine hepatitis virus-1 pneumonia model.Frontiers in immunology · 2023Article
- Fibronectin leucine-rich transmembrane protein 2 drives monocyte differentiation into macrophagesFrontiers in immunology · 2023Article
- Chondroitin Sulfate Proteoglycan 4 as a Marker for Aggressive Squamous Cell Carcinoma.Cancers · 2022Review
Corrections and comments
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Authors and funding
15 authors at 5 institutions in 5 countries.
Funding
Abstract
Blood vessel abnormalization alters cancer cell metabolism and promotes cancer dissemination and metastasis. However, the biological features of the abnormalized blood vessels that facilitate cancer progression and whether they can be targeted therapeutically have not been fully investigated. Here, we found that an axon guidance molecule, fibronectin leucine-rich transmembrane protein 2 (FLRT2), is expressed preferentially in abnormalized vessels of advanced colorectal cancers in humans and that its expression correlates negatively with long-term survival. Endothelial cell-specific deletion of Flrt2 in mice selectively pruned abnormalized vessels, resulting in a unique metabolic state termed "oxygen-glucose uncoupling," which suppressed tumor metastasis. Moreover, Flrt2 deletion caused an increase in the number of mature vessels, resulting in a significant increase in the antitumor effects of immune checkpoint blockers. Mechanistically, we found that FLRT2 forms noncanonical interendothelial adhesions that safeguard against oxidative stress through homophilic binding. Together, our results demonstrated the existence of tumor-specific interendothelial adhesions that enable abnormalized vessels to facilitate cancer aggressiveness. Targeting this type of adhesion complex could be a safe and effective therapeutic option to suppress cancer 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.