It has been demonstrated that Klotho inhibits the activation of NF-κB. Remarkably, overexpressing Klotho in Caco-2 cells sensitized the TRAIL death receptor DR4 and impeded cell proliferation by promoting apoptosis. Furthermore, an increase in KL expression suppressed tumor growth and invasion, primarily through the inhibition of the IGF1R-mediated PI3K/Akt pathway in colon cancer cells. This evidence concerns the gene NFKB1 and colonic neoplasm.