In colorectal tumors and colon cancer cell lines, the Ras oncogenic activation reduces Sef expression very early during the oncogenesis, thus driving the aberrant nuclear accumulation of phosphorylated MEK1/2 and ERK1/2, which leads to ERK1/2 signaling hyperactivation, which, in turn, causes cell-cycle dysregulation, increased cell proliferation, polyploidization and neoplastic transformation. This evidence concerns the gene MAPK3 and colorectal neoplasm.