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Updated: Apr 23, 2026

An Oncogenic Hepatocyte-Induced Orthotopic Mouse Model of Hepatocellular Cancer Arising in the Setting of Hepatic Inflammation and Fibrosis
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Dysregulated serum response factor triggers formation of hepatocellular carcinoma

Stefan Ohrnberger1, Abhishek Thavamani, Albert Braeuning

  • 1Department for Molecular Biology, Interfaculty Institute of Cell Biology, Tuebingen University, Germany.

Hepatology (Baltimore, Md.)
|October 1, 2014
PubMed
Abstract

Insights

Serum response factor (SRF) drives hepatocellular carcinoma (HCC) through Ras/MAPK and Rho/actin signaling. Inhibiting both pathways may offer a novel HCC treatment strategy.

Area of Science:

  • Molecular biology
  • Oncology
  • Hepatology

Background:

  • Serum response factor (SRF) is a key regulator of genes involved in cell proliferation and survival.
  • Ras/MAPK and Rho/actin signaling pathways are frequently activated in hepatocellular carcinoma (HCC).
  • Understanding the role of SRF in HCC pathogenesis is crucial for developing effective therapies.

Purpose of the Study:

  • To investigate the role of constitutively active SRF in hepatocarcinogenesis.
  • To determine if SRF activation can drive the development of HCC.
  • To explore the molecular mechanisms by which SRF contributes to HCC development.

Main Methods:

  • Generation of SRF-VP16iHep mice with conditional expression of active SRF in hepatocytes.
  • Analysis of liver nodules and HCC development in these mice.
  • Transcriptomic and epigenomic analysis of murine and human HCCs.

Main Results:

  • SRF-VP16iHep mice developed hyperproliferative liver nodules progressing to lethal HCC.
  • Murine HCCs acquired Ctnnb1 mutations, mirroring human HCC.
  • Transcriptional profiles of murine HCCs resembled a subgroup of human HCCs with activated oncofetal genes and Igf2/H19 hypomethylation.

Conclusions:

  • Convergent Ras/MAPK and Rho/actin signaling driven by SRF is a potent oncogenic mechanism in hepatocarcinogenesis.
  • Simultaneous inhibition of Ras/MAPK and Rho/actin signaling represents a potential therapeutic strategy for HCC.

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