ArticleProceedings of the National Academy of Sciences of the United States of America2012
Phenotype-based high-content chemical library screening identifies statins as inhibitors of in vivo lymphangiogenesis.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 39 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.
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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
39 citing papers in PubMed, 68 citations in OpenAlex.
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- Evaluation of the Effect of Botulinum Toxin A on the Lymphatic Endothelial Cells.Aesthetic plastic surgery · 2024Article
- Angiogenesis-on-a-chip coupled with single-cell RNA sequencing reveals spatially differential activations of autophagy along angiogenic sprouts.Nature communications · 2024Article
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- Molecular Profiling of Lymphatic Endothelial Cell Activation In Vitro.International journal of molecular sciences · 2023Article
- An Introduction to Chemogenomics.Methods in molecular biology (Clifton, N.J.) · 2023Article
- The natural FGF-trap long pentraxin 3 inhibits lymphangiogenesis and lymphatic dissemination.Experimental hematology & oncology · 2022Article
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- The lymphatic vasculature: An active and dynamic player in cancer progression.Medicinal research reviews · 2022Review
- Oxidatively Modified LDL Suppresses Lymphangiogenesis via CD36 Signaling.Antioxidants (Basel, Switzerland) · 2021Article
- LETR1 is a lymphatic endothelial-specific lncRNA governing cell proliferation and migration through KLF4 and SEMA3C.Nature communications · 2021Article
- Tissue-resident macrophages regulate lymphatic vessel growth and patterning in the developing heart.Development (Cambridge, England) · 2021Article
- Biomaterial Based Strategies for Engineering New Lymphatic Vasculature.Advanced healthcare materials · 2020Review
- A zebrafish genetic model enables an invaluable discovery: a lifesaving treatment for a lymphatic anomaly.Lab animal · 2019Article
- CSgator: an integrated web platform for compound set analysis.Journal of cheminformatics · 2019Article
- Non-coding RNAs as Regulators of Lymphangiogenesis in Lymphatic Development, Inflammation, and Cancer Metastasis.Frontiers in oncology · 2019Review
- Glycogen synthase kinase 3-β inhibition induces lymphangiogenesis through β-catenin-dependent and mTOR-independent pathways.PloS one · 2019Article
- Article
- Role of simvastatin in tumor lymphangiogenesis and lymph node metastasis.Clinical & experimental metastasis · 2018Article
Corrections and comments
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Authors and funding
9 authors at 3 institutions in 2 countries.
Funding
Abstract
Lymphangiogenesis plays an important role in promoting cancer metastasis to sentinel lymph nodes and beyond and also promotes organ transplant rejection. We used human lymphatic endothelial cells to establish a reliable three-dimensional lymphangiogenic sprouting assay with automated image acquisition and analysis for inhibitor screening. This high-content phenotype-based assay quantifies sprouts by automated fluorescence microscopy and newly developed analysis software. We identified signaling pathways involved in lymphangiogenic sprouting by screening the Library of Pharmacologically Active Compounds (LOPAC)(1280) collection of pharmacologically relevant compounds. Hit characterization revealed that mitogen-activated protein kinase kinase (MEK) 1/2 inhibitors substantially block lymphangiogenesis in vitro and in vivo. Importantly, the drug class of statins, for the first time, emerged as potent inhibitors of lymphangiogenic sprouting in vitro and of corneal and cutaneous lymphangiogenesis in vivo. This effect was mediated by inhibition of the 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase and subsequently the isoprenylation of Rac1. Supplementation with the enzymatic products of HMG-CoA reductase functionally rescued lymphangiogenic sprouting and the recruitment of Rac1 to the plasma membrane.
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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.