ArticleDisease models & mechanisms2015
Phenotype-driven chemical screening in zebrafish for compounds that inhibit collective cell migration identifies multiple pathways potentially involved in metastatic invasion.
Article in Disease models & mechanisms, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.
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Who cites it
31 citing papers in PubMed, 51 citations in OpenAlex.
- A high-resolution phenotypic screen identifies regulators of CNS axon diameter in zebrafish.PLoS biology · 2026Article
- Zebrafish swimming towards cures: a scalable NAM platform for drug discovery.Drug discovery today · 2026Review
- Review
- Article
- Emerging Drug Targets for Endometriosis.Biomolecules · 2022Review
- Learning the rules of collective cell migration using deep attention networks.PLoS computational biology · 2022Article
- Tipping the Scales With Zebrafish to Understand Adaptive Tumor Immunity.Frontiers in cell and developmental biology · 2021Review
- Article
- Machine learning discriminates a movement disorder in a zebrafish model of Parkinson's disease.Disease models & mechanisms · 2020Article
- Morphological landscape of endothelial cell networks reveals a functional role of glutamate receptors in angiogenesis.Scientific reports · 2020Article
- Zebrafish-Based Screening Models for the Identification of Anti-Metastatic Drugs.Molecules (Basel, Switzerland) · 2020Review
- Expanding the CRISPR Toolbox in Zebrafish for Studying Development and Disease.Frontiers in cell and developmental biology · 2019Review
- Fishing forward and reverse: Advances in zebrafish phenomics.Mechanisms of development · 2018Review
- Hedgehog signaling regulates cell motility and optic fissure and stalk formation during vertebrate eye morphogenesis.Development (Cambridge, England) · 2018Article
- The Air Sac Primordium ofInternational journal of molecular sciences · 2018Review
- A High-Content Screen Reveals New Small-Molecule Enhancers of Ras/Mapk Signaling as Probes for Zebrafish Heart Development.Molecules (Basel, Switzerland) · 2018Article
- Review
- Mib1 contributes to persistent directional cell migration by regulating the Ctnnd1-Rac1 pathway.Proceedings of the National Academy of Sciences of the United States of America · 2017Article
- LITTLE FISH, BIG DATA: ZEBRAFISH AS A MODEL FOR CARDIOVASCULAR AND METABOLIC DISEASE.Physiological reviews · 2017Review
- Development of a zebrafish sepsis model for high-throughput drug discovery.Molecular medicine (Cambridge, Mass.) · 2017Article
Corrections and comments
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Authors and funding
9 authors at 3 institutions in 1 country.
Funding
Abstract
In the last decade, high-throughput chemical screening has become the dominant approach for discovering novel compounds with therapeutic properties. Automated screening using in vitro or cultured cell assays have yielded thousands of candidate drugs for a variety of biological targets, but these approaches have not resulted in an increase in drug discovery despite major increases in expenditures. In contrast, phenotype-driven screens have shown a much stronger success rate, which is why we developed an in vivo assay using transgenic zebrafish with a GFP-marked migrating posterior lateral line primordium (PLLp) to identify compounds that influence collective cell migration. We then conducted a high-throughput screen using a compound library of 2160 annotated bioactive synthetic compounds and 800 natural products to identify molecules that block normal PLLp migration. We identified 165 compounds that interfere with primordium migration without overt toxicity in vivo. Selected compounds were confirmed in their migration-blocking activity by using additional assays for cell migration. We then proved the screen to be successful in identifying anti-metastatic compounds active in vivo by performing orthotopic tumor implantation assays in mice. We demonstrated that the Src inhibitor SU6656, identified in our screen, can be used to suppress the metastatic capacity of a highly aggressive mammary tumor cell line. Finally, we used CRISPR/Cas9-targeted mutagenesis in zebrafish to genetically validate predicted targets of compounds. This approach demonstrates that the migrating PLLp in zebrafish can be used for large-scale, high-throughput screening for compounds that inhibit collective cell migration and, potentially, anti-metastatic compounds.
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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.