SMAD4 and colorectal carcinoma: In the case of CRC, Pandurangan et al. and Smit et al. mentioned that the main signaling pathways affected in CRC epithelial cells are: the APC, KRAS, transforming growth factor-β (TGF-β/Sma genes and the Drosophila Mad (SMAD4), protein 53 (P53), Wingless-related integration site (Wnt)/β-catenin, YAP/Transcriptional co-activator with PDZ-binding motif (TAZ) hippo signaling, Rho-family, Tumor necrosis factor-α (TNF-α), and phosphoinositide 3-kinase (PI3k) pathways, which are known by the adenoma-carcinoma sequence (ACS) [3,127].