SMAD3 and breast cancer: However, it was reported that functional differences exist between structurally similar Smad2 and Smad3 with respect to their target genes [21, 22], selective R-Smad deficiency leading to defects in embryonic development [23-25], Smad3 but not Smad2 dependent promotion of EMT in keratinocytes [26] and metastasis in breast cancer cells [27].