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Endostatin is a potential inhibitor of Wnt signaling. J Cell Biol 2002 Aug 05;158(3):529-39

Date

07/31/2002

Pubmed ID

12147676

Pubmed Central ID

PMC2173844

DOI

10.1083/jcb.200203064

Abstract

Endostatin (ES) is a fragment of collagen XVIII that possesses antiangiogenic activity. To gain insight into ES-mediated signaling, we studied the effects of ES RNA on Xenopus embryogenesis and observed developmental abnormalities consistent with impaired Wnt signaling. ES RNA blocked the axis duplication induced by beta-catenin, partially suppressed Wnt-dependent transcription, and stimulated degradation of both wild-type and "stabilized" forms of beta-catenin, the latter suggesting that ES signaling does not involve glycogen synthase kinase 3. Moreover, ES uses a pathway independent of the Siah1 protein in targeting beta-catenin for proteasome-mediated degradation. ES failed to suppress the effects of T cell-specific factor (TCF)-VP16 (TVP), a constitutive downstream transcriptional activator that acts independently of beta-catenin. Importantly, these data were replicated in endothelial cells and also in the DLD-1 colon carcinoma cells with the mutated adenomatous polyposis coli protein. Finally, suppression of endothelial cell migration and inhibition of cell cycle by ES were reversed by TVP. Though high levels of ES were used in both the Xenopus and endothelial cell studies and the effects on beta-catenin signaling were modest, these data argue that at pharmacological concentrations ES may impinge on Wnt signaling and promote beta-catenin degradation.

Author List

Hanai J, Gloy J, Karumanchi SA, Kale S, Tang J, Hu G, Chan B, Ramchandran R, Jha V, Sukhatme VP, Sokol S

Author

Ramani Ramchandran PhD Professor in the Pediatrics department at Medical College of Wisconsin




MESH terms used to index this publication - Major topics in bold

Angiogenesis Inhibitors
Animals
Body Patterning
Cell Movement
Collagen
Collagen Type XVIII
Cytoskeletal Proteins
Endostatins
Endothelium, Vascular
Female
Gene Expression Regulation, Developmental
Growth Substances
Heparan Sulfate Proteoglycans
Humans
Mutation
Neovascularization, Pathologic
Nuclear Proteins
Oocytes
Peptide Fragments
Protein Structure, Tertiary
Proto-Oncogene Proteins
RNA, Messenger
S Phase
Signal Transduction
Trans-Activators
Tumor Cells, Cultured
Ubiquitin-Protein Ligases
Wnt Proteins
Xenopus Proteins
Xenopus laevis
Zebrafish Proteins
beta Catenin
jenkins-FCD Prod-484 8aa07fc50b7f6d102f3dda2f4c7056ff84294d1d