Related Experiment Video

Updated: Oct 3, 2025

In Vitro Cultivation Techniques for Modeling Liver Organogenesis, Building Assembloids, and Designing Synthetic Tissues using Human Cell Lines
08:50

In Vitro Cultivation Techniques for Modeling Liver Organogenesis, Building Assembloids, and Designing Synthetic Tissues using Human Cell Lines

Published on: April 18, 2025

592

FOXD3 and GAB2 as a pair of rivals antagonistically control hepatocellular carcinogenesis

Ruimin Liu1, Yan Sun1, Shuai Chen1

  • 1School of Pharmaceutical Sciences, State Key Laboratory of Cellular Stress Biology, Xiamen University, Xiamen, China.

The FEBS Journal
|February 18, 2022
PubMed

Insights

The tumor suppressor Forkhead box D3 (Foxd3) inhibits the growth-promoting gene GAB2 in liver cancer. This mutual inhibition offers a new therapeutic strategy for hepatocellular carcinoma (HCC).

Area of Science:

  • Oncology
  • Molecular Biology
  • Genetics

Background:

  • GAB2 was previously identified as a promoter of hepatocellular carcinoma (HCC) tumorigenesis.
  • Understanding the regulatory mechanisms of GAB2 is crucial for developing targeted HCC therapies.

Purpose of the Study:

  • To investigate the role of Forkhead box D3 (Foxd3) as a transcriptional regulator of the GAB2 gene in HCC.
  • To elucidate the functional relationship between Foxd3 and GAB2 in HCC development.

Main Methods:

  • Analysis of FOXD3 and GAB2 expression in human HCC cells.
  • In vitro studies involving ectopic Foxd3 expression in HCC cells.
  • Western blot analysis to assess protein phosphorylation (Jak2, Stat3).
  • Examination of Foxd3 and Gab2 protein levels in a mouse model of diethylnitrosamine (DEN)-induced HCC.

Main Results:

  • Foxd3 acts as a transcriptional repressor of the Gab2 gene.
  • Low FOXD3 and high GAB2 expression were observed in human HCC cells.
  • Increased Foxd3 expression inhibited Gab2 expression, cell proliferation, and migration in vitro.
  • Foxd3 suppressed Gab2-stimulated Jak2 and Stat3 phosphorylation.
  • A negative correlation between Foxd3 and Gab2 protein levels was observed in HCC tissues.

Conclusions:

  • Foxd3 functions as a tumor suppressor by inhibiting GAB2 in HCC.
  • The reciprocal inhibition between Foxd3 and Gab2 plays a synergistic role in HCC occurrence.
  • Targeting this Foxd3-Gab2 axis presents a novel therapeutic avenue for hepatocellular carcinoma.
Keywords:
Foxd3Gab2hepatocellular carcinoma

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