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Updated: Feb 27, 2026

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Nrf2 Mutagenic Activation Drives Hepatocarcinogenesis

Hoang Kieu Chi Ngo1, Do-Hee Kim1, Young-Nam Cha2

  • 1Tumor Microenvironment Global Core Research Center, College of Pharmacy, Seoul National University, Seoul, South Korea.

Cancer Research
|June 29, 2017
PubMed

Insights

Nrf2 (Nuclear factor erythroid 2-related factor 2) deficiency prevents liver cancer development in mice. Blocking Nrf2 may offer a new strategy for treating hepatocellular carcinoma (HCC).

Area of Science:

  • Oncology
  • Molecular Biology
  • Biochemistry

Background:

  • Hepatocellular carcinoma (HCC) is a major global cancer burden.
  • Nuclear factor erythroid 2-related factor 2 (Nrf2) regulates oxidative stress and is a potential target for HCC prevention.

Purpose of the Study:

  • To investigate the role of Nrf2 in diethylnitrosamine (DEN)-induced liver cancer in mice.
  • To elucidate the mechanisms by which Nrf2 influences hepatocarcinogenesis.

Main Methods:

  • Utilized Nrf2-deficient mice and diethylnitrosamine (DEN) induction model.
  • Analyzed Nrf2 expression, nuclear translocation, and transcriptional activity in liver tumors.
  • Assessed the impact of Nrf2 disruption on pentose phosphate pathway enzymes and Keap1 binding.

Main Results:

  • Nrf2-deficient mice showed resistance to DEN-induced liver cancer.
  • Nrf2 expression and activity were elevated in liver tumors, promoting hepatoma growth.
  • Nrf2 genetic disruption decreased pentose phosphate pathway enzymes, correlating with reduced HCC incidence.
  • Enhanced Nrf2 activity was linked to altered binding of its inhibitor, Keap1.

Conclusions:

  • Overactivated Nrf2 is crucial for the growth of DEN-induced hepatocellular carcinoma.
  • Nrf2 blockade presents a potential therapeutic strategy for preventing and treating liver cancer.

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