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The paradoxical role of Nrf2 in tumor biology

Hui Shen1, Suna Zhou, Jiansheng Wang

  • 1Department of Thoracic Oncosurgery, First Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, China.

Critical Reviews in Eukaryotic Gene Expression
|April 6, 2013
PubMed

Insights

Nuclear factor erythroid 2-related factor 2 (Nrf2) acts as a cell protector but also promotes tumor progression. Its paradoxical role in cancer is influenced by the tumor microenvironment, particularly hypoxia.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cell Biology

Background:

  • Nuclear factor erythroid 2-related factor 2 (Nrf2) is a transcription factor regulating antioxidant and detoxification enzymes.
  • Nrf2 and its downstream genes are frequently overexpressed in human tumors, exhibiting a dual role in normal cell protection and malignant progression.

Purpose of the Study:

  • To review the dual role of Nrf2 as a tumor suppressor or oncogene in various cancer stages.
  • To investigate the influence of the tumor microenvironment, specifically hypoxia, on Nrf2's function in cancer.

Main Methods:

  • Literature review of recent studies on Nrf2 in cancer.
  • Analysis of Nrf2's role in tumor initiation, invasion, and metastasis.
  • Examination of the impact of oxidative stress and hypoxia on Nrf2 activity.

Main Results:

  • Nrf2 mutations in Keap1 or Nrf2 genes under oxidative stress promote tumor initiation.
  • Hypoxia in later tumor stages affects Nrf2 activity, influencing angiogenesis, invasion, and metastasis.
  • Nrf2's downstream genes involved in angiogenesis are upregulated under hypoxic conditions.

Conclusions:

  • Nrf2 exhibits context-dependent roles in cancer, acting as a suppressor or oncogene.
  • The hypoxic tumor microenvironment is a critical determinant of Nrf2's function in malignant progression.
  • Understanding Nrf2's paradoxical roles is crucial for developing effective cancer therapies.

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