A theme emerging during the past few years is that members of the
small leucine-rich proteoglycan gene family affect cell growth by interacting with multiple
receptor tyrosine kinases (RTKs), mostly by a physical down-regulation of the receptors, thereby depriving
tumor cells of pro-survival signals.
Decorin binds and down-regulates several RTKs, including Met, the receptor for
hepatocyte growth factor. Here we demonstrate that
decorin blocks several biological activities mediated by the Met signaling axis, including cell scatter, evasion, and migration. These effects were mediated by a profound down-regulation of noncanonical β-
catenin levels. In addition, Myc, a downstream target of β-
catenin, was markedly down-regulated by
decorin, whereas phosphorylation of Myc at
threonine 58 was markedly induced. The latter is known to destabilize Myc and target it for proteasomal degradation. We also discovered that systemic delivery of
decorin using three distinct
tumor xenograft models caused down-regulation of Met and a concurrent suppression of β-
catenin and Myc levels. We found that
decorin protein core labeled with the near infrared
dye IR800 specifically targeted the
tumor cells expressing Met. Even 68-h post-injection,
decorin was found to reside within the
tumor xenografts with little or no binding to other tissues. Collectively, our results indicate a role for a secreted
proteoglycan in suppressing the expression of key oncogenic factors required for
tumor progression.