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A Multiplexed Luciferase-based Screening Platform for Interrogating Cancer-associated Signal Transduction in Cultured Cells
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The Multifaceted Roles of NRF2 in Cancer: Friend or Foe?

Christophe Glorieux1, Cinthya Enríquez2,3, Constanza González2

  • 1State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou 510060, China.

Antioxidants (Basel, Switzerland)
|January 22, 2024
PubMed

Insights

The nuclear factor erythroid 2-related factor 2 (NRF2) pathway regulates cellular antioxidant systems. This review explores NRF2

Area of Science:

  • Molecular Biology
  • Cellular Biology
  • Oncology

Background:

  • Reactive oxygen species (ROS) are crucial in cellular processes but implicated in disease pathogenesis when excessive.
  • Nuclear factor erythroid 2-related factor 2 (NRF2) is a key transcription factor controlling cellular antioxidant responses.
  • The NRF2 pathway, including its regulator Kelch-like ECH-associated protein 1 (KEAP1), is extensively studied for its role in cancer.

Purpose of the Study:

  • To examine the role of phase separation in activating NRF2 transcriptional activity.
  • To explore the dual role of NRF2 in cancer promotion and prevention.
  • To discuss therapeutic strategies involving NRF2 modulation in cancer treatment.

Main Methods:

  • Literature review of existing research on NRF2, oxidative stress, and cancer.
  • Analysis of studies investigating phase separation in NRF2 activation.
  • Synthesis of findings on NRF2's impact on tumor immunology, cancer stem cells, metastasis, and LncRNAs.

Main Results:

  • NRF2 participates in dysregulated cell proliferation, metabolic remodeling, and apoptosis resistance.
  • Phase separation is identified as a mechanism for activating NRF2 transcriptional activity.
  • NRF2 exhibits multifaceted roles, influencing cancer stem cells, metastasis, tumor immunology, and LncRNAs.

Conclusions:

  • NRF2 plays a complex, dual role in cancer, acting as both a tumor suppressor and promoter.
  • Understanding NRF2's regulation, including phase separation, is crucial for cancer therapy.
  • Modulating NRF2 therapeutically presents advantages, disadvantages, and limitations that require careful consideration.
Keywords:
LncRNANRF2NRF2 activatorsNRF2 inhibitorscancermetabolismmetastasisnatural compoundsphase separationtumor immunology

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