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SOCS1 controls liver regeneration by regulating HGF signaling in hepatocytes

Yirui Gui1, Mehdi Yeganeh, Sheela Ramanathan

  • 1Immunology Division, Department of Pediatrics, Université de Sherbrooke, Centre de Recherche Clinique Etienne-Le Bel, Centre Hospitalier de l'Université de Sherbrooke, Sherbrooke, Québec, Canada J1H 5N4.

Journal of Hepatology
|June 28, 2011
PubMed
Abstract

Insights

Suppressor of cytokine signaling 1 (SOCS1) restrains hepatocyte growth factor (HGF) signaling, suggesting SOCS1 acts as a liver tumor suppressor by inhibiting c-Met pathways.

Area of Science:

  • Hepatology
  • Molecular Biology
  • Oncology

Background:

  • Hepatocellular carcinoma (HCC) frequently shows SOCS1 gene repression.
  • SOCS1 deficiency increases susceptibility to liver cancer, indicating a tumor suppressor role.
  • Mechanisms of SOCS1's tumor suppression in the liver are not fully understood.

Purpose of the Study:

  • Investigate SOCS1's role in hepatocyte proliferation.
  • Determine SOCS1's function in liver regeneration after partial hepatectomy.
  • Elucidate SOCS1's impact on hepatocyte growth factor (HGF) signaling.

Main Methods:

  • Utilized Socs1(-/-)Ifng(-/-) mice for liver regeneration studies.
  • Examined signaling pathways downstream of IL-6 and HGF receptors.
  • Assessed SOCS1 interaction with the HGF receptor c-Met.

Main Results:

  • Socs1(-/-)Ifng(-/-) mice showed accelerated liver regeneration and DNA synthesis.
  • Hepatocytes lacking SOCS1 exhibited enhanced HGF-induced proliferation, migration, and c-Met/Gab1 phosphorylation.
  • SOCS1 overexpression reduced HGF-induced proliferation, migration, and ERK1/2 phosphorylation in hepatoma cells.

Conclusions:

  • SOCS1 attenuates c-Met signaling, negatively regulating HGF signaling.
  • Inhibition of HGF signaling by SOCS1 is a key anti-tumor mechanism in the liver.

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