The Role of The βklotho Gene, Fgf21 and Fgfr1 in Cancerogenesis

Abstract

Klotho was discovered in 1997 as an anti-aging gene that, when overexpressed, may extend the life span, but when it is disrupted, it may be a factor responsible for premature aging syndrome. The structure and the role of αKlotho and βKlotho genes from Klotho family in malignant tumors is described. The expression profile of the βKlotho gene is significantly different from the expression of the αKlotho gene. Analysis of Klotho expression in breast cancer, cervical cancer as well as endometrial cancer are discussed. The available data indicate the involvement of βKlotho in the neoplastic transformation of the endometrium. More advanced disease is related to negative expression of βKlotho gene. Fibroblast growth factors (FGFs) are a large family of proteins characterized by different functions in the cell development and metabolism. The FGF signaling is also associated with cancerogenesis. The relation between some FGF subfamilies and endometrial cancer clinical data is reported. The interaction between FGF subfamilies and the Klotho subfamily proteins acting as a co-receptor is stressed. Disorders in signaling of the FGF / FGFR pathway have been confirmed in gynecology. It can be assumed that increased expression of FGF21 might be a suppressor factor in endometrial cancer. The FGF21 factor, like the βKlotho protein, achieves its biological effect via the FGFR1 receptor. High expression of the FGFR1 gene inhibits further tumor growth. FGFR1 has the potential to perform both a suppressor and promoter role in the oncogenesis process.