HGF upregulation contributes to angiogenesis in mice with keratinocyte-specific Smad2 deletion.

ABSTRACT: TGF-β signaling can promote tumor formation and development or suppress it, depending on the cellular context and tumor stage. A potential target of this dual effect of TGF-β is HGF, as TGF-β can inhibit or promote its expression, although the mechanisms underlying this are largely unknown. In the present study, we found that mice with keratinocyte-specific deletion of the TGF-β signaling mediator Smad2 (referred to herein as K5.Smad2(-/-) mice), which have increased susceptibility to squamous cell carcinomas (SCCs), exhibited angiogenesis associated with epithelial overexpression of HGF and endothelial activation of the HGF receptor c-Met. Application of a c-Met inhibitor abrogated angiogenesis, suggesting that HGF overexpression plays a major role in angiogenesis associated with epitheli

SUBMITTER: Hoot KE 

PROVIDER: S-EPMC2947237 | biostudies-literature | 2010 Oct

REPOSITORIES: biostudies-literature