Dysregulation in IGF-1R, FGFR4 and beta Klotho signaling in patients with medullary thyroid cancer

Abstract

BACKGROUND: Medullary thyroid cancer (MTC) is a relatively rare thyroid neoplasm derived from neuroendocrine C cells which secrete calcitonin. alpha Klotho (alpha KL) and beta Klotho (beta KL) are transmembrane proteins which modulate different signaling systems, such as endocrine FGFs and IGF1 pathways. Dysregulation of the FGF19/FGFR4/beta KL and IGF-1/IGF-1R/alpha KL signaling axes has been implicated in the pathogenesis of several cancers. However, their role in the pathogenesis of MTC has not been determined. METHODS: The aim of this study was to assess alpha KL, beta KL, FGF19, IGF-1, FGFR4, and IGF-1R concentrations in a group of 11 patients with medullary thyroid cancer (MTC). The control group consisted of 20 healthy volunteers. Serum concentrations of these factors were measured using specific ELISA methods. RESULTS: Significantly lower concentrations of beta KL and higher concentrations of FGFR4 and IGF-1R were found in patients with MTC as compared to controls. CONCLUSIONS: Our results indicate that a disrupted signaling pathway for beta KL, FGFR4 and IGF-1R may play a role in the development of medullary thyroid cancers. However, further studies are required to confirm these findings and to use this knowledge in clinical practice.