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

Neuro Endocrinol Lett. 2019 Mar;40(1):29-35.


Background: Medullary thyroid cancer (MTC) is a relatively rare thyroid neoplasm derived from neuroendocrine C cells which secrete calcitonin. αKlotho (αKL) and βKlotho (βKL) are transmembrane proteins which modulate different signaling systems, such as endocrine FGFs and IGF1 pathways. Dysregulation of the FGF19/FGFR4/βKL and IGF-1/IGF-1R/αKL 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 αKL, βKL, 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 βKL 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 βKL, 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.

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Carcinoma, Medullary / blood*
  • Carcinoma, Medullary / pathology
  • Female
  • Humans
  • Male
  • Membrane Proteins / blood*
  • Middle Aged
  • Receptor, Fibroblast Growth Factor, Type 4 / blood*
  • Receptor, IGF Type 1 / blood*
  • Signal Transduction / physiology*
  • Thyroid Neoplasms / blood*
  • Thyroid Neoplasms / pathology
  • Young Adult


  • KLB protein, human
  • Membrane Proteins
  • FGFR4 protein, human
  • Receptor, Fibroblast Growth Factor, Type 4
  • Receptor, IGF Type 1