Home | Help | Feedback | Subscriptions | Archive | Search | Table of Contents

This Article Full Text (PDF, 208K) PPT slides of all figures Alert me when this article is cited Services Email this article Similar articles in this journal Alert me to new content in the JCB Download to citation manager Citing Articles Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Dove, A. W. Search for Related Content PubMed Articles by Dove, A. W. Related Collections Related Article Social Bookmarking                            What's this?

© The Rockefeller University Press, 0021-9525/2002/8/383-b $5.00
The Journal of Cell Biology, Volume 158, Number 3, August 5, 2002 383-b-383

A new path for endostatin

Endostatin (right) prevents secondary axis induction by ß-catenin (left).

The ability of endostatin to inhibit angiogenesis has produced sensational headlines, but efforts to understand how this collagen fragment actually works have drawn considerably less fanfare. On page 529, Hanai et al. now demonstrate that endostatin acts through a novel pathway to inhibit Wnt signaling, suggesting that the effects of endostatin on tumors may be more complex than previously thought.

Using Xenopus embryonic development as a model system, the authors found that high concentrations of endostatin produced developmental abnormalities characteristic of Wnt signaling defects, a notion that was confirmed in cultured mammalian cells. Endostatin seems to act through a novel pathway to target ß-catenin, a mediator of Wnt signaling, for proteasomal degradation. A downstream transcriptional activator that acts independently of ß-catenin rescues cells from two of the effects of endostatin: cell cycle arrest and inhibition of endothelial cell migration.

The new work raises the possibility that endostatin may have direct antitumor effects, mediated by the inhibition of Wnt signaling, in addition to its antiangiogenic activity. The results also implicate Wnt and ß-catenin in the regulation of endothelial cell migration and cell cycle progression, suggesting that downstream effectors of this pathway might be promising targets for future cancer therapies.

Alan W. Dove

alanwdove{at}earthlink.net

CiteULike    Complore    Connotea    Del.icio.us    Digg    Facebook    Reddit    Technorati    Twitter    What's this?

Related Article

Endostatin is a potential inhibitor of Wnt signaling

Jun-ichi Hanai, Joachim Gloy, S. Ananth Karumanchi, Sujata Kale, Jian Tang, Guang Hu, Barden Chan, Ramani Ramchandran, Vivek Jha, Vikas P. Sukhatme, and Sergei Sokol
J. Cell Biol. 2002 158: 529-539. [Abstract] [Full Text] [PDF]

This Article Full Text (PDF, 208K) PPT slides of all figures Alert me when this article is cited Services Email this article Similar articles in this journal Alert me to new content in the JCB Download to citation manager Citing Articles Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Dove, A. W. Search for Related Content PubMed Articles by Dove, A. W. Related Collections Related Article Social Bookmarking                            What's this?