Background: The Klotho gene was originally identified as an anti-aging gene in 1997. Recent studies have demonstrated aberrant expression of Klotho in a number of cancers, including breast cancer, lung cancer, hepatocellular carcinoma (HCC), and so on.
Methods: A literature search focusing on dysregulation of Klotho and its possible mechanisms in cancer was performed.
Results and conclusions: Downregulation of Klotho was found in several cancers, such as pancreatic cancer, HCC, and other tumors. Epigenetic modulation, such as promoter methylation and histone deacetylation, also contributed to the dysregulation of Klotho in cancers. Downregulation of Klotho resulted in promoted proliferation and reduced apoptosis of cancer cells. The relevant mechanisms include the fibroblast growth factor signaling, the insulin-like growth factor 1 receptor pathway, and the Wnt/β-catenin signaling pathway. Furthermore, the Klotho protein hopefully provides new insights into cancer target treatment.