CCN2 and breast carcinoma: To determine the contributing role of SMAD4 in SIRT7-regulated TGF-β signaling, we employed MDA-MB-468 cells, a breast cancer cell line lacking SMAD4. As shown, the expression of TGF-β responsive genes like p15, p21, PAI1, CTGF, and SMAD7 was not affected by SIRT7 KD (Fig. 7a), which was restored by the reconstitution of ectopic SMAD4 (Fig. 7b; Supplementary Fig. 11a).