Functionally, TGF-β inhibited proliferation and tumorigenesis process; however, during colon cancer cells development, TGF-β signaling was to suppress the effect of tumor suppressor so that TGF-β (TGFβR1 and TGFβR2) or intracellular mediator of SMAD (SMAD4, SMAD2, and SMAD3) were failed in inactivating cancer cells (Yushan et al., 2018). This evidence concerns the gene SMAD4 and malignant colon neoplasm.