Related Experiment Video

Updated: Jun 26, 2026

A Three-Dimensional Spheroid Model to Investigate the Tumor-Stromal Interaction in Hepatocellular Carcinoma
12:24

A Three-Dimensional Spheroid Model to Investigate the Tumor-Stromal Interaction in Hepatocellular Carcinoma

Published on: September 30, 2021

Molecular insights for targeting the Nrf1 pathway in hepatocellular carcinoma

Xi Chen1, Zhengwen Zhang2, Siqian Cui3,4

  • 1The Laboratory of Cell Biochemistry and Topogenetic Regulation, College of Bioengineering & Chongqing Academy of Medical Sciences, Chongqing General Hospital, Faculty of Medicine, Chongqing University, Chongqing, China.

Expert Opinion on Therapeutic Targets
|June 25, 2026
PubMed
Abstract

Insights

Nuclear factor erythroid 2-related factor 1 (Nrf1) has dual roles in liver cancer, acting as both a tumor suppressor and a promoter. Understanding its complex regulation is key for developing new hepatocellular carcinoma (HCC) therapies.

Area of Science:

  • Molecular Biology
  • Oncology
  • Cellular Homeostasis

Background:

  • Nuclear factor erythroid 2-related factor 1 (Nrf1) is crucial for cellular homeostasis, redox balance, and mitochondrial function.
  • Nrf1 exhibits complex, dual roles in hepatocellular carcinoma (HCC), acting as both a tumor suppressor and a driver of progression.
  • Its function is intertwined with Nrf2, another key regulator in cellular defense pathways.

Purpose of the Study:

  • To systematically review the molecular-cellular regulatory network of Nrf1 in HCC.
  • To elucidate the functional divergence and synergy between Nrf1 and Nrf2 in the context of HCC.
  • To analyze the evolving research landscape of Nrf1 in HCC, including its dual roles, isoform specificity, and therapeutic potential.

Main Methods:

  • Systematic literature review and analysis of existing research on Nrf1 in HCC.
  • Examination of molecular and cellular regulatory networks governing Nrf1 function.
  • Comparative analysis of Nrf1 and Nrf2 roles and interactions in HCC.

Main Results:

  • Nrf1's function in HCC is complex, with evidence supporting both tumor-suppressive and tumor-promoting activities.
  • Nrf1's roles are influenced by its isoforms, post-translational modifications, and interactions with Nrf2.
  • The balance between Nrf1 and Nrf2 (Yin-Yang) is critical in HCC development and progression.

Conclusions:

  • Targeting Nrf1 for HCC therapy presents significant challenges due to its complex and context-dependent roles.
  • Future research should focus on Nrf1 isoform specificity, post-translational modifications, and the Nrf1/Nrf2 balance.
  • Developing Nrf1 modulators could offer novel therapeutic strategies by enhancing anti-cancer defense mechanisms.
Keywords:
DDI2Hepatocellular carcinomaNGLY1Nrf1/NFE2L1Nrf2/NFE2L2TCF11Yin-Yang ruleredox stress

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