HNF4A and malignant colon neoplasm: Other mechanisms have been proposed that attempt to explain the mechanism for S100A4 overexpression: i) by hypomethylation, since increased S100A4 expression levels have been associated with decreased methylation of the first intron of this gene in cell lines and carcinomas of pancreatic origin [26] and of the second intron in colon cancer cell lines [41]; and ii) through the Wnt signaling pathway, given that it has been shown that S100A4 is a target of this pathway in colon cancer and a functional TCF binding site has been identified in its promoter sequence [18].