Figure 7.

Schematic representation of BGN- and DCN-mediated inhibition of the TGF-β pathway and restriction of HER-2/neu signaling. TGF-β1 binds to its receptors (TGF-βRI and TGF-βR2) and induces phosphorylation of TACE, resulting in its translocation to the cell surface, where TACE induces integrins and cleaves EGFR pro-ligands. EGFR ligands will initiate autocrine and paracrine EGFR signaling, which is amplified in HER2-overexpressing cells (BGN^low/neg HER-2/neu⁺ cells). In BGN^high HER-2/neu⁺ cells, BGN and DCN bind to TGF-β1 and restricts HER-2/neu signaling, thus allowing tumor suppression to occur.