SMAD3 and neoplasm: Moreover, the RAC1B-TGFβ1-SMAD3 pathway may extend to epithelial genes other than CDH1 as we observed positive regulation by TGFB1 of GRHL2 and OVOL2. Both genes encode transcription factors that control the expression of CDH1 [28], regulate epithelial morphogenesis, differentiation and plasticity [29], and suppress EMT-driven tumor progression in part via a reciprocal feedback loop with ZEB1 [30,31].