<> "The repository administrator has not yet configured an RDF license."^^ . <> . . "Investigation on endothelial junctional remodeling by the tankyrase inhibitor XAV939"^^ . "Tankyrase inhibitors are recognized as potential therapeutics for malignancies that exhibit increased intrinsic β-catenin activity. Nevertheless, the specific mechanism of tankyrase inhibition effects on the endothelium after systemic administration remains inadequately understood. In this study, we aimed to explore the effects of the tankyrase inhibitor XAV939 on endothelial cells (EC) function and elucidate the associated underlying mechanism. The analysis of EC function involved in sprouting angiogenesis, EC migration, junctional dynamics, endothelial permeability assay by human umbilical vein endothelial cells (HUVEC) monolayer, and ex vivo explanted mouse retina as main experimental models. The investigation of signaling mechanisms involved multiple experimental techniques, including western blot analysis, immunofluorescence (IF) staining, quantitative polymerase chain reaction (qPCR) in both HUVEC and HEK293 cells, and luciferase reporter gene assays in HEK293 cells. XAV939 treatment results in changed junctional dynamics phenotype, permeability function, and endothelial migration defects. Mechanically, XAV939 treatment enhanced the stability of angiomotin-like proteins 1 and 2 (AMOTL1 and 2), which inhibits the process of YAP/TAZ nuclear localization, ultimately leading to the suppression of TEAD-mediated transcription. Interestingly, XAV939 treatment has been found to interfere with AJs by activating the RhoA-Rho dependent kinase (ROCK)-mediated F-actin bundling. Conversely, the impeding of F-actin bundling caused by the ROCK inhibitor H1152 has been shown to restore the normal functioning of ECs. Surprisingly, this mechanism was associated increase in nuclear TAZ and TEAD-mediated transcription, indicating distinct regulation of YAP and TAZ by cytoskeleton in EC. \r\nIn conclusion, this study provides a comprehensive understanding of junctional remodeling interplay among the actin cytoskeleton, EC function and YAP/TAZ signaling, and underlying mechanism during tankyrase inhibitor systemic administration."^^ . "2024" . . . . . . "Nan"^^ . "Ma"^^ . "Nan Ma"^^ . . . . . . "Investigation on endothelial junctional remodeling by the tankyrase inhibitor XAV939 (PDF)"^^ . . . "Investigation on endothelial junctional remodeling by the tankyrase inhibitor XAV939 Nan Ma.pdf"^^ . . . "Investigation on endothelial junctional remodeling by the tankyrase inhibitor XAV939 (Other)"^^ . . . . . . "indexcodes.txt"^^ . . . "Investigation on endothelial junctional remodeling by the tankyrase inhibitor XAV939 (Other)"^^ . . . . . . "lightbox.jpg"^^ . . . "Investigation on endothelial junctional remodeling by the tankyrase inhibitor XAV939 (Other)"^^ . . . . . . "preview.jpg"^^ . . . "Investigation on endothelial junctional remodeling by the tankyrase inhibitor XAV939 (Other)"^^ . . . . . . "medium.jpg"^^ . . . "Investigation on endothelial junctional remodeling by the tankyrase inhibitor XAV939 (Other)"^^ . . . . . . "small.jpg"^^ . . "HTML Summary of #35615 \n\nInvestigation on endothelial junctional remodeling by the tankyrase inhibitor XAV939\n\n" . "text/html" . . . "610 Medizin"@de . "610 Medical sciences Medicine"@en . .