ArticleCell reports2013
The calcineurin-NFAT-angiopoietin-2 signaling axis in lung endothelium is critical for the establishment of lung metastases.
Article in Cell reports, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 57 papers.
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Who cites it
57 citing papers in PubMed, 113 citations in OpenAlex.
- Systemic counterregulatory response of angiopoietin-2 after aflibercept therapy for nAMD: a potential escape mechanism.Acta ophthalmologica · 2021Trial
- Evaluation of Angiopoietin-2 as a biomarker in gastric cancer: results from the randomised phase III AVAGAST trial.British journal of cancer · 2016Trial
- A dual-pronged host-directed therapeutic targeting cyclophilin A and pathogenic interferon response abrogates virus-triggered pregnancy pathologies.Nature communications · 2026Article
- LMO1 expression in neuroblastoma cells reprograms tumor-associated macrophages to promote metastasis.iScience · 2026Article
- Calcineurin-NFAT-DSCR1.4 signaling as druggable axis in Gαq-R183Q-driven capillary malformations.Angiogenesis · 2026Article
- Protein serine/threonine phosphatases in tumor microenvironment: a vital player and a promising therapeutic target.Theranostics · 2025Review
- PPP3CB overexpression mediates EGFR TKI resistance in lung tumors via calcineurin/MEK/ERK signaling.Life science alliance · 2024Article
- Role of Protein Phosphatases in Tumor Angiogenesis: Assessing PP1, PP2A, PP2B and PTPs Activity.International journal of molecular sciences · 2024Review
- Epigenetic regulation of breast cancer metastasis.Cancer metastasis reviews · 2024Review
- mir-605-3p prevents liver premetastatic niche formation by inhibiting angiogenesis via decreasing exosomal nos3 release in gastric cancer.Cancer cell international · 2024Article
- Short Term Effect of Pre-Operative Anti-VEGF on Angiogenic and Fibrotic Profile of Fibrovascular Membranes of Proliferative Diabetic Retinopathy.Investigative ophthalmology & visual science · 2024Article
- Activin A from primary breast tumors generates a pre-metastatic niche by inducing pulmonary fibrosis.Translational breast cancer research : a journal focusing on translational research in breast cancer · 2024Article
- AP-1-independent NFAT signaling maintains follicular T cell function in infection and autoimmunity.The Journal of experimental medicine · 2023Article
- Article
- Isolation and characterization of ZK002, a novel dual function snake venom protein fromFrontiers in pharmacology · 2023Article
- Evaluation of Expression Levels of NFATc2 and PPARG Genes Two Effector Elements of WNT Pathway in Non-Small Cell Lung Carcinoma.Advanced biomedical research · 2023Article
- RCAN1-mediated calcineurin inhibition as a target for cancer therapy.Molecular medicine (Cambridge, Mass.) · 2022Review
- Transcriptional analysis of lung fibroblasts identifies PIM1 signaling as a driver of aging-associated persistent fibrosis.JCI insight · 2022Article
- Decoding the Phosphatase Code: Regulation of Cell Proliferation by Calcineurin.International journal of molecular sciences · 2022Review
- Cancer-associated fibroblasts facilitate premetastatic niche formation through lncRNA SNHG5-mediated angiogenesis and vascular permeability in breast cancer.Theranostics · 2022Article
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Authors and funding
10 authors at 3 institutions in 2 countries.
Funding
Abstract
The premetastatic niche is a predetermined site of metastases, awaiting the influx of tumor cells. However, the regulation of the angiogenic switch at these sites has not been examined. Here, we demonstrate that the calcineurin and nuclear factor of activated T cells (NFAT) pathway is activated specifically in lung endothelium prior to the detection of tumor cells that preferentially metastasize to the lung. Upregulation of the calcineurin pathway via deletion of its endogenous inhibitor Dscr1 leads to a significant increase in lung metastases due to increased expression of a newly identified NFAT target, Angiopoietin-2 (ANG2). Increased VEGF levels specifically in the lung, and not other organ microenvironments, trigger a threshold of calcineurin-NFAT signaling that transactivates Ang2 in lung endothelium. Further, we demonstrate that overexpression of DSCR1 or the ANG2 receptor, soluble TIE2, prevents the activation of lung endothelium, inhibiting lung metastases in our mouse models. Our studies provide insights into mechanisms underlying angiogenesis in the premetastatic niche and offer targets for lung metastases.
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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.