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Decorin is a novel antagonistic ligand of the Met receptor.

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 (K(d) = approximately 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 = approximately 6 min). Decorin suppresses intracellular levels of beta-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.

Pubmed ID: 19433454

Authors

  • Goldoni S
  • Humphries A
  • Nyström A
  • Sattar S
  • Owens RT
  • McQuillan DJ
  • Ireton K
  • Iozzo RV

Journal

The Journal of cell biology

Publication Data

May 18, 2009

Associated Grants

  • Agency: NCI NIH HHS, Id: R01 CA039481
  • Agency: NCI NIH HHS, Id: R01 CA120975
  • Agency: NCI NIH HHS, Id: R01 CA39481
  • Agency: NCI NIH HHS, Id: R01 CA47282

Mesh Terms

  • Binding, Competitive
  • Cell Proliferation
  • Decorin
  • Extracellular Matrix Proteins
  • Half-Life
  • HeLa Cells
  • Humans
  • Ligands
  • Neoplasm Metastasis
  • Neoplasms
  • Protein Binding
  • Proteoglycans
  • Proto-Oncogene Proteins c-cbl
  • Proto-Oncogene Proteins c-met
  • beta Catenin