With the recognition that various genes responsible for collagen synthesis and fibroblastic phenotypic transformation are activated by TGF-β1 in Smad3-dependent manner [136], it’s been uncovered that the global hypermethylation especially promoter hypermethylation-associated SMAD3 silencing could be attributed to the neoplastic transformation in lung cancer [104], and DNMT3B-catalyzed hypermethylation at miR-200 s promoter could establish CAF activation by sustaining autocrine TGF-β1 in breast cancer [137]. Here, SMAD3 is linked to breast cancer.