ArticleStem cell reports2016
Identification of RSK and TTK as Modulators of Blood Vessel Morphogenesis Using an Embryonic Stem Cell-Based Vascular Differentiation Assay.
Article in Stem cell reports, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.
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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
7 citing papers in PubMed, 18 citations in OpenAlex.
- The role of N6-methyladenosine modification in tumor angiogenesis.Frontiers in oncology · 2024Review
- Phosphotyrosine picked threonine kinase stimulates proliferation of human osteosarcoma cellsArchives of medical science : AMS · 2022Article
- Substituted pteridinones, pyrimidines, pyrrolopyrimidines, and purines as p90 ribosomal S6 protein kinase-2 (RSK2) inhibitors: Pharmacophore modeling data.Data in brief · 2021Article
- Ribosomal S6 protein kinase 4 promotes radioresistance in esophageal squamous cell carcinoma.The Journal of clinical investigation · 2020Article
- Adaptive RSK-EphA2-GPRC5A signaling switch triggers chemotherapy resistance in ovarian cancer.EMBO molecular medicine · 2020Article
- Molecular docking of substituted pteridinones and pyrimidines to the ATP-binding site of the N-terminal domain of RSK2 and associated MM/GBSA and molecular field datasets.Data in brief · 2020Article
- Article
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Authors and funding
12 authors at 4 institutions in 1 country.
Funding
Abstract
Blood vessels are formed through vasculogenesis, followed by remodeling of the endothelial network through angiogenesis. Many events that occur during embryonic vascular development are recapitulated during adult neoangiogenesis, which is critical to tumor growth and metastasis. Current antiangiogenic tumor therapies, based largely on targeting the vascular endothelial growth factor pathway, show limited clinical benefits, thus necessitating the discovery of alternative targets. Here we report the development of a robust embryonic stem cell-based vascular differentiation assay amenable to small-molecule screens to identify novel modulators of angiogenesis. In this context, RSK and TTK were identified as angiogenic modulators. Inhibition of these pathways inhibited angiogenesis in embryoid bodies and human umbilical vein endothelial cells. Furthermore, inhibition of RSK and TTK reduced tumor growth, vascular density, and improved survival in an in vivo Lewis lung carcinoma mouse model. Our study suggests that RSK and TTK are potential targets for antiangiogenic therapy, and provides an assay system for further pathway screens.
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Registered trials
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