SMAD4 and neoplasm: Tumor cells induce CAFs formation through the TGF-β/SMAD pathway, whereby free TGF-β secreted by tumor cells binds to TGF-β I and II receptors in fibroblasts, prompting downstream SMAD2 and SMAD3 phosphorylation and further forming a complex with SMAD4, resulting in up-regulation of α-SMA transcription30.