SMAD4 and breast neoplasm: Sirt7 overexpression suppresses S-phase kinase-associated protein 2 (Skp2)-Culin1-F-box (SCF) E3 ligase-mediated AKT ubiquitination and TGF-β/SMAD family member 4 (SMAD4) signaling, thus antagonizing the growth of breast tumors and metastasis to distal organs (94, 96).