As mentioned above, monoubiquitination of SMAD4 blocks the interaction of SMAD4 with phospho-SMAD2 (Figure 3c), and the deubiquitinase USP9X reverses this PTM to activate TGF-β signaling, which in turn promotes migration and metastasis of breast cancer cells [84,86]. Here, TGFB1 is linked to breast cancer.