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, Renato V. Iozzo

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161 Scopus citations

Abstract

Decorin, a member of the small leucine-rich proteoglycan gene family, impedes tumor cell growth by down-regulating the epidermal growth factor receptor. Decorin has a complex binding repertoire, thus, we predicted that decorin would modulate the bioactivity of other tyrosine kinase receptors. We discovered that decorin binds directly and with high affinity (Kd = ∼1.5 nM) to Met, the receptor for hepatocyte growth factor (HGF). Binding of decorin to Met is efficiently displaced by HGF and less efficiently by internalin B, a bacterial Met ligand. Interaction of decorin with Met induces transient receptor activation, recruitment of the E3 ubiquitin ligase c-Cbl, and rapid intracellular degradation of Met (half-life = ∼6 min). Decorin suppresses intracellular levels of β-catenin, a known downstream Met effector, and inhibits Met-mediated cell migration and growth. Thus, by antagonistically targeting multiple tyrosine kinase receptors, decorin contributes to reduction in primary tumor growth and metastastic spreading.

Original languageEnglish (US)
Pages (from-to)743-754
Number of pages12
JournalJournal of Cell Biology
Volume185
Issue number4
DOIs
StatePublished - May 18 2009

All Science Journal Classification (ASJC) codes

  • Cell Biology

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    Goldoni, S., Humphries, A., Nyström, A., Sattar, S., Owens, R. T., McQuillan, D. J., Ireton, K., & Iozzo, R. V. (2009). Decorin is a novel antagonistic ligand of the Met receptor. Journal of Cell Biology, 185(4), 743-754. https://doi.org/10.1083/jcb.200901129