Mechanistically, NSDHL knockdown impaired the cancer stemness characteristics of BCSCs by suppressing TGF-β signaling, which in turn decreased the secretion of TGF-β 1 and TGF-β3, inactivated Smad2 and Smad3, and downregulated the expression of SOX2 and NANOG, key regulators of cancer stemness (Fig. 6C). Here, SMAD2 is linked to cancer.