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Dysregulation of the Keap1-Nrf2 pathway in cancer

Hanna M Leinonen1, Emilia Kansanen1, Petri Pölönen2

  • 1Department of Biotechnology and Molecular Medicine, A.I. Virtanen Institute for Molecular Sciences, University of Eastern Finland, PO Box 1627, FIN-70211 Kuopio, Finland.

Biochemical Society Transactions
|November 10, 2015
PubMed

Insights

The Keap1-Nrf2 pathway is crucial in cancer, with cancer cells hijacking it to promote growth and resistance. Understanding these dysregulation mechanisms is key for developing new cancer therapies.

Area of Science:

  • Molecular Biology
  • Oncology
  • Biochemistry

Background:

  • The Kelch-like ECH-associated protein 1 (Keap1)-nuclear factor E2-related factor 2 (Nrf2) pathway is frequently dysregulated in cancer.
  • Constitutively active Nrf2 leads to increased expression of cytoprotective genes, contributing to cancer progression.

Purpose of the Study:

  • To review the mechanisms of increased Nrf2 activity in cancer.
  • To highlight findings from multi-omics projects across various cancer types.

Main Methods:

  • Literature review focusing on cancer biology and molecular pathways.
  • Analysis of data from large-scale multi-omics projects.

Main Results:

  • Cancer cells exploit the Keap1-Nrf2 system through various mechanisms.
  • Hijacked Nrf2 activity enhances chemo- and radio-resistance, proliferation, and metabolic reprogramming.
  • Nrf2 dysregulation also contributes to apoptosis inhibition in cancer cells.

Conclusions:

  • Dysregulation of the Keap1-Nrf2 pathway is a significant factor in cancer development and progression.
  • Targeting the Keap1-Nrf2 system presents a potential therapeutic strategy for cancer treatment.
Keywords:
Kelch-like ECH-associated protein 1 (Keap1)The Cancer Genome Atlas (TCGA)cancergenomenuclear factor E2-related factor 2 (Nrf2)oxidative stress

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