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Decorin has Met a new receptor

Decorin binds to the Met receptor (green) and causes its internalization (arrows).

A small extracellular matrix protein called decorin blocks multiple growth factor receptors in order to inhibit tumor formation, suggest Goldoni et al.

Mice lacking decorin are more susceptible to cancers, whereas increased levels of the protein can inhibit tumor growth and metastasis. Decorin was originally found to bind collagen fibers and regulate their assembly, but it can also inhibit EGF signaling by binding to and down-regulating the EGF receptor. Goldoni et al. wondered whether decorin might be even more promiscuous, and bind to other receptor tyrosine kinases as well.

The researchers screened 42 different receptors, and found that decorin also targeted Met—the receptor for the growth factor HGF, which promotes proliferation and invasion when constitutively activated in cancer cells. Although binding to decorin briefly activated Met, this only led to the receptor's rapid down-regulation via two different pathways—by degradation inside the cell and by the cleavage and release of its extracellular domain. According to senior author Renato Iozzo, decorin is therefore the first known antagonist of Met signaling.

Treating cells with decorin also caused the destruction of a downstream effector of Met called β-catenin, stimulated apoptosis, and reduced cell motility. This latter effect relied on decorin's ability to inhibit the EGF receptor as well as Met. Iozzo thinks that decorin could be a new way to treat cancers, which often have increased levels of multiple growth factor receptors and can survive therapies that only target a single pathway.

References

Goldoni, S., et al. 2009. J. Cell Biol. doi:10.1083/jcb.200901129.[Abstract/Free Full Text]

bshort{at}rockefeller.edu

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Decorin is a novel antagonistic ligand of the Met receptor

Silvia Goldoni, Ashley Humphries, Alexander Nyström, Sampurna Sattar, Rick T. Owens, David J. McQuillan, Keith Ireton, and Renato V. Iozzo
J. Cell Biol. 2009 185: 743-754. [Abstract] [Full Text] [PDF]

This Article Full Text (PDF, 489K) 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 Short, B. Search for Related Content PubMed Articles by Short, B. Related Collections Related Article Social Bookmarking                            What's this?