SMAD4 inactivation can drive the development of metastatictraits in a subset of CRC cases, but a system-wide study of the effectsof SMAD4 inactivation on the molecular mechanisms and related biologicalprocesses that contribute to CRC progression was not performed yet.In this study, we applied a multiomics approach to study the molecularconsequences of SMAD4 inactivation in advanced CRC at the transcriptome,proteome, and secretome levels. This evidence concerns the gene SMAD4 and colorectal carcinoma.