Fig. 6
From: Proteolysis-targeting chimeras (PROTACs) in cancer therapy
PROTACs targeting cancer metastasis. Activation of Integrin/FAK/PI3K/AKT, TGF-β/SMAD and Wnt/β-catenin pathways significantly increase the expression of pro-EMT transcription factors (e.g. ZEB, SNAIL and TWIST), leading to the downregulation of E-cadherin (E-Cad) that maintains epithelial integrity, and the upregulation of N-cadherin (N-Cad) and vimentin (VIM) that implicate in motility and invasion. These key elements involved in metastasis can be targeted by PROTACs (red arrow). Tumor-suppressor proteins are indicated in blue and oncogenic proteins are indicated in red. In the presented pathways, PROTACs have been developed targeting FAK [246, 247], IGF-1R [248], p38 [249, 250], Smad3 [251], Src [248, 252], TCF [253], TGF-β1 [254] and β-catenin [255]