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NRF2 and STAT3: friends or foes in carcinogenesis?

Andrea Arena1, Maria Anele Romeo1, Rossella Benedetti1

  • 1Department of Experimental Medicine, Sapienza University of Rome, Viale Regina Elena 324, 00161, Rome, Italy.

Discover Oncology
|March 31, 2023
PubMed

Insights

Nuclear factor erythroid 2-related factor 2 (NRF2) and Signal transducer and activator of transcription 3 (STAT3) are key transcription factors in cancer. Their complex interplay influences tumor growth, immune suppression, and response to therapy.

Area of Science:

  • Molecular Biology
  • Cancer Biology
  • Cellular Signaling

Background:

  • Nuclear factor erythroid 2-related factor 2 (NRF2) is a transcription factor crucial in cancer development and survival pathways.
  • Signal transducer and activator of transcription 3 (STAT3) is frequently activated in cancer, promoting tumorigenesis and immune evasion.

Purpose of the Study:

  • To explore the intricate relationship between NRF2 and STAT3 in the context of cancer.
  • To understand how their cross-talk influences cancer progression and the tumor microenvironment.

Main Methods:

  • This perspective synthesizes existing research on NRF2 and STAT3 interactions.
  • It reviews their regulation by endoplasmic reticulum (ER) stress and the unfolded protein response (UPR).
  • It examines their roles in DNA damage response (DDR) and heat shock proteins (HSPs).

Main Results:

  • NRF2 and STAT3 signaling pathways are interconnected and influence each other.
  • Their cross-talk is modulated by autophagy, cytokines, and ER stress/UPR activation.
  • Both transcription factors regulate DNA damage response (DDR) and heat shock protein (HSP) expression.

Conclusions:

  • The complex networking of NRF2 and STAT3 significantly impacts cancer biology.
  • Further research into their interactions is essential for developing novel and effective cancer therapies.
  • Understanding this interplay could reveal new therapeutic targets for improved cancer treatment strategies.
Keywords:
CytokinesDDRNRF2STAT3p62/SQSTM1

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