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Abbreviated Journal Title

J. Cell Biol.

Keywords

Epidermal-Growth-Factor; Tyrosine Kinase; Beta-Catenin; C-Met; Down-Regulation; In-Vivo; Listeria-Monocytogenes; Breast-Cancer; Signal-Transduction; Mammalian-Cells; Cell Biology

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 (K(d) = similar to 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 = similar to 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.

Journal Title

Journal of Cell Biology

Volume

185

Issue/Number

4

Publication Date

1-1-2009

Document Type

Article

Language

English

First Page

743

Last Page

754

WOS Identifier

WOS:000266279900017

ISSN

0021-9525

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