One hypothesis is that before metastasis develops, many CRC cells undergo DNA hypermethylation on the CXCL12 promoter [99], such that autocrine and paracrine CXCL12 signaling is reduced and tumor cells can migrate along a gradient that leads them to distant organs, known to highly express the chemokine [47]. This evidence concerns the gene CXCL12 and colorectal carcinoma.