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

Research output: Contribution to journalArticle

150 Citations (Scopus)

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

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Decorin
Ligands
Receptor Protein-Tyrosine Kinases
Growth
Proto-Oncogene Proteins c-met
Catenins
Ubiquitin-Protein Ligases
Hepatocyte Growth Factor
Epidermal Growth Factor Receptor
Cell Movement
Half-Life
Neoplasms

All Science Journal Classification (ASJC) codes

  • Cell Biology

Cite this

Goldoni, S., Humphries, A., Nyström, A., Sattar, S., Owens, R. T., McQuillan, D. J., ... 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
Goldoni, Silvia ; Humphries, Ashley ; Nyström, Alexander ; Sattar, Sampurna ; Owens, Rick T. ; McQuillan, David J. ; Ireton, Keith ; Iozzo, Renato V. / Decorin is a novel antagonistic ligand of the Met receptor. In: Journal of Cell Biology. 2009 ; Vol. 185, No. 4. pp. 743-754.
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Goldoni, S, Humphries, A, Nyström, A, Sattar, S, Owens, RT, McQuillan, DJ, Ireton, K & Iozzo, RV 2009, 'Decorin is a novel antagonistic ligand of the Met receptor', Journal of Cell Biology, vol. 185, no. 4, pp. 743-754. https://doi.org/10.1083/jcb.200901129

Decorin is a novel antagonistic ligand of the Met receptor. / Goldoni, Silvia; Humphries, Ashley; Nyström, Alexander; Sattar, Sampurna; Owens, Rick T.; McQuillan, David J.; Ireton, Keith; Iozzo, Renato V.

In: Journal of Cell Biology, Vol. 185, No. 4, 18.05.2009, p. 743-754.

Research output: Contribution to journalArticle

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Goldoni S, Humphries A, Nyström A, Sattar S, Owens RT, McQuillan DJ et al. Decorin is a novel antagonistic ligand of the Met receptor. Journal of Cell Biology. 2009 May 18;185(4):743-754. https://doi.org/10.1083/jcb.200901129