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Updated: Feb 8, 2026

A Simple and Efficient Method to Detect Nuclear Factor Activation in Human Neutrophils by Flow Cytometry
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Activation of p62/SQSTM1-Keap1-Nuclear Factor Erythroid 2-Related Factor 2 Pathway in Cancer

Yoshinobu Ichimura1, Masaaki Komatsu1

  • 1Department of Biochemistry, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan.

Frontiers in Oncology
|June 23, 2018
PubMed

Insights

Autophagy and the Keap1-Nrf2 system are crucial for cellular defense. The p62-Keap1-Nrf2 pathway links these systems, but can promote cancer growth and drug resistance via Nrf2 activation.

Area of Science:

  • Cellular Biology
  • Molecular Biology
  • Cancer Research

Background:

  • Autophagy and the Keap1-Nrf2 system are key cellular defense mechanisms against metabolic and oxidative stress.
  • These systems are interconnected through the p62-Keap1-Nrf2 pathway, involving the phosphorylation of p62/SQSTM1.
  • While protective in normal cells, this pathway is increasingly implicated in cancer development and progression.

Purpose of the Study:

  • To investigate the dual role of the p62-Keap1-Nrf2 pathway in cellular defense and tumorigenesis.
  • To elucidate the mechanisms by which this pathway promotes cancer cell growth, drug resistance, and metabolic reprogramming.
  • To explore the potential of targeting p62/SQSTM1 for cancer chemotherapy.

Main Methods:

  • The study likely involved molecular biology techniques to analyze protein interactions and signaling pathways.
  • Investigated the role of autophagy impairment in cancer malignancy.
  • Examined the impact of Nrf2 activation on tumor cell metabolism and drug resistance.

Main Results:

  • The p62-Keap1-Nrf2 pathway, while protective in normal cells, can drive tumorigenesis in pre-malignant cells.
  • Nrf2 activation within this pathway promotes tumor growth and drug resistance through metabolic reprogramming.
  • Impaired autophagy is associated with cancer malignancy and tumor maintenance.

Conclusions:

  • The p62-Keap1-Nrf2 pathway has a context-dependent role, promoting cancer under certain conditions.
  • p62/SQSTM1 represents a potential therapeutic target for cancers characterized by its overexpression.
  • Targeting this pathway could offer new strategies for cancer treatment, particularly in overcoming drug resistance.
Keywords:
Keap1–nuclear factor erythroid 2-related factor 2 systemcancermetabolic reprogrammingp62/SQSTM1selective autophagy

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