Increased vascularity and spontaneous metastasis of breast cancer by hedgehog signaling mediated upregulation of cyr61.

ABSTRACT: The Hedgehog (Hh) pathway is well known for its involvement in angiogenesis and vasculogenesis during ontogeny. The ligand, Sonic Hh (SHH), has an important role in vascular formation during development. However, SHH expression is upregulated on tumor cells and can impact the tumor microenvironment. We have investigated the effects of autocrine as well as paracrine Hh signaling on tumor cells as well as on endothelial cells, respectively. Upon constitutive expression of SHH, breast cancer cells showed aggressive behavior and rapid xenograft growth characterized by highly angiogenic tumors that were spontaneously metastatic. In these cells, SHH caused activation of the Hh transcription factor, GLI1, leading to upregulated expression of the potent pro-angiogenic secreted molecule, CYR61 (cys

SUBMITTER: Harris LG 

PROVIDER: S-EPMC3276742 | biostudies-literature | 2012 Jul

REPOSITORIES: biostudies-literature