# Tyrosine hydroxylase inhibits HCC progression by downregulating TGFβ/Smad signaling

## TL;DR

This study shows that tyrosine hydroxylase (TH) helps prevent liver cancer progression by blocking a key signaling pathway.

## Contribution

The study reveals a new non-metabolic role of TH in inhibiting HCC through TGFβ/Smad signaling.

## Key findings

- Lower TH levels in HCC patients correlate with worse outcomes like larger tumors and higher AFP levels.
- TH inhibits HCC cell growth and metastasis by phosphorylating serine residues S19/S40.
- TH binds to Smad2 and blocks TGFβ/Smad signaling activation.

## Abstract

The alteration of metabolic processes has been found to have significant impacts on the development of hepatocellular carcinoma (HCC). Nevertheless, the effects of dysfunction of tyrosine metabolism on the development of HCC remains to be discovered. This research demonstrated that tyrosine hydroxylase (TH), which responsible for the initial and limiting step in the bio-generation of the neuro-transmitters dopamine and adrenaline, et al. was shown to be reduced in HCC. Increased expression of TH was found facilitates the survival of HCC patients. In addition, decreased TH indicated larger tumor size, much more numbers of tumor, higher level of AFP, and the presence of cirrhosis. TH effectively impairs the growth and metastasis of HCC cells, a process dependent on the phosphorylation of serine residues (S19/S40). TH directly binds to Smad2 and hinders the cascade activation of TGFβ/Smad signaling with the treatment of TGFβ1. In summary, our study uncovered the non-metabolic functions of TH in the development of HCC and proposes that TH might be a promising biomarker for diagnosis as well as an innovative target for metastatic HCC.

The online version contains supplementary material available at 10.1186/s40001-024-01703-z.