The functional operation of an ALK2-SMAD1/5-SMAD4-RUNX3 axis activated, i.e., by BMP7, which counteracts the canonical ALK5-SMAD2/3-SMAD4 signaling, may underly the opposing roles and potential antagonistic mechanisms between the BMP7 and TGFβ pathways in cancer [3,5,6]. This evidence concerns the gene SMAD4 and cancer.