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An Oncogenic Hepatocyte-Induced Orthotopic Mouse Model of Hepatocellular Cancer Arising in the Setting of Hepatic Inflammation and Fibrosis
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NUPR1, a new target in liver cancer: implication in controlling cell growth, migration, invasion and sorafenib

M R Emma1,2, J L Iovanna3, D Bachvarov4,5

  • 1Institute of Biomedicine and Molecular Immunology "Alberto Monroy", National Research Council (CNR), Palermo, Italy.

Cell Death & Disease
|June 24, 2016
PubMed

Insights

Nuclear protein 1 (NUPR1) promotes hepatocellular carcinoma (HCC) growth and sorafenib resistance. Targeting the NUPR1/RELB/IER3/RUNX2 pathway may offer new HCC treatment strategies.

Area of Science:

  • Oncology
  • Molecular Biology
  • Hepatology

Background:

  • Sorafenib is the sole approved treatment for advanced hepatocellular carcinoma (HCC), yet its efficacy is limited.
  • The precise mechanisms underlying sorafenib's action and resistance in HCC remain incompletely understood.
  • Nuclear protein 1 (NUPR1), a stress-inducible protein overexpressed in cancers, has an unclear role in HCC.

Purpose of the Study:

  • To investigate the role of NUPR1 in HCC development and progression.
  • To determine the involvement of NUPR1 in sorafenib treatment response in HCC.
  • To elucidate the molecular pathways regulated by NUPR1 in HCC.

Main Methods:

  • NUPR1 expression analysis in human HCC samples.
  • In vitro and in vivo studies involving NUPR1 knockdown in HCC cells.
  • Gene expression profiling and network analysis following NUPR1 silencing.
  • Assessment of the impact of RELB, IER3, and RUNX2 gene silencing on HCC cells.

Main Results:

  • NUPR1 expression is significantly elevated in HCC tissues compared to normal liver.
  • NUPR1 knockdown enhances HCC cell sensitivity to sorafenib and inhibits proliferation, migration, and invasion.
  • NUPR1 silencing downregulates key genes including RELB, IER3, and RUNX2, impacting pathways like NF-κB and ERK.
  • Silencing of RELB, IER3, or RUNX2 individually inhibits HCC cell viability and growth.

Conclusions:

  • The NUPR1/RELB/IER3/RUNX2 pathway plays a critical role in hepatocarcinogenesis.
  • NUPR1 promotes HCC progression and contributes to sorafenib resistance.
  • Targeting the NUPR1 pathway presents a promising therapeutic strategy for managing HCC.

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