Understanding the structure-function relationship between FGF19 and its mitogenic and metabolic activities.

Area of Science:

• Endocrinology
• Oncology
• Molecular Biology

Background:

• Fibroblast Growth Factor 19 (FGF19) functions as an endocrine hormone due to low heparan sulfate proteoglycan binding.
• FGF19 regulates metabolic activities and signals through FGF receptors, similar to classical FGFs.
• Aberrant FGF signaling is linked to tumor development, with FGF19 implicated in hepatocellular carcinoma.

Purpose of the Study:

• To review advances in understanding the structure-function relationship of FGF19 and its interactions with FGF receptors (FGFRs).
• To discuss the physiological activities of FGF19 and its distinctions from FGF21.
• To explore strategies for separating FGF19's mitogenic and metabolic activities for therapeutic development.

Main Methods:

• Review of current literature on FGF19 structure-function, signaling pathways, and physiological roles.
• Analysis of studies investigating FGF19's role in tumorigenesis, including mouse models.
• Examination of therapeutic strategies involving anti-FGF19 antibodies and FGFR4 inhibition.

Main Results:

• FGF19's unique binding properties enable endocrine function.
• FGF19 signaling through FGFRs, particularly FGFR4 in the liver, is implicated in hepatocellular carcinoma.
• Anti-FGF19 antibody treatment demonstrated suppression of tumor progression in preclinical models.

Conclusions:

• FGF19 plays a dual role in metabolic regulation and potential tumorigenesis.
• FGFR4 is a key receptor in FGF19-mediated liver cancer development.
• Developing therapeutic molecules that selectively target FGF19's activities is a promising strategy for cancer treatment.